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  1. Diversity Analysis of the Immunoglobulin M Heavy Chain Gene in ...

    African Journals Online (AJOL)

    A full-length cDNA encoding the immunoglobulin (IgM) heavy chain gene of Nile tilapia was successfully cloned using the 5' and 3' RACE techniques. The complete cDNA of the Nile tilapia IgM heavy chain gene is 1,921 bp in length and has an open reading frame (ORF) of 1,740 bp, which corresponds to 580 amino acid ...

  2. Fungicidal activity of peptides encoded by immunoglobulin genes

    OpenAIRE

    Polonelli, Luciano; Ciociola, Tecla; Sperind?, Martina; Giovati, Laura; D?Adda, Tiziana; Galati, Serena; Travassos, Luiz R.; Magliani, Walter; Conti, Stefania

    2017-01-01

    Evidence from previous works disclosed the antimicrobial, antiviral, anti-tumour and/or immunomodulatory activity exerted, through different mechanisms of action, by peptides expressed in the complementarity-determining regions or even in the constant region of antibodies, independently from their specificity and isotype. Presently, we report the selection, from available databases, of peptide sequences encoded by immunoglobulin genes for the evaluation of their potential biological activitie...

  3. Molecular Analysis of Activation-Induced Cytidine Deaminase Gene in Immunoglobulin-E Deficient Patients

    Directory of Open Access Journals (Sweden)

    Sergio Roa

    2008-01-01

    Full Text Available Understanding how class switch recombination (CSR is regulated to produce immunoglobulin E (IgE has become fundamental because of the dramatic increase in the prevalence of IgE-mediated hypersensitivity reactions. CSR requires the induction of the enzyme AICDA in B cells. Mutations in AICDA have been linked to Hyper-IgM syndrome (HIGM2, which shows absence of switching to IgE as well as to IgG and IgA. Although isolated IgE deficiency is a rare entity, here we show some individuals with normal serum IgM, IgG, and IgA levels that had undetectable total serum IgE levels. We have analyzed the AICDA gene in these individuals to determine if there are mutations in AICDA that could lead to selective IgE deficiency. Conformational sensitive gel electrophoresis (CSGE and sequencing analysis of AICDA coding sequences demonstrated sequence heterogeneity due to 5923A/G and 7888C/T polymorphisms, but did not reveal any novel mutation that might explain the selective IgE deficit.

  4. Biased immunoglobulin light chain gene usage in the shark1

    Science.gov (United States)

    Iacoangeli, Anna; Lui, Anita; Naik, Ushma; Ohta, Yuko; Flajnik, Martin; Hsu, Ellen

    2015-01-01

    This study of a large family of kappa light (L) chain clusters in nurse shark completes the characterization of its classical immunoglobulin (Ig) gene content (two heavy chain classes, mu and omega, and four L chain isotopes, kappa, lambda, sigma, and sigma-2). The shark kappa clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over a ~500 bp interval, and functional clusters are widely separated by at least 100 kb. Six out of ca. 39 kappa clusters are pre-rearranged in the germline (GL-joined). Unlike the complex gene organization and multistep assembly process of Ig in mammals, each shark Ig rearrangement, somatic or in the germline, appears to be an independent event localized to the minigene. This study examined the expression of functional, non-productive, and sterile transcripts of the kappa clusters compared to the other three L chain isotypes. Kappa cluster usage was investigated in young sharks, and a skewed pattern of split gene expression was observed, one similar in functional and non-productive rearrangements. These results show that the individual activation of the spatially distant kappa clusters is non-random. Although both split and GL-joined kappa genes are expressed, the latter are prominent in young animals and wane with age. We speculate that, in the shark, the differential activation of the multiple isotypes can be advantageously used in receptor editing. PMID:26342033

  5. Immunoglobulin gene usage in the human anti-pathogen response.

    Science.gov (United States)

    Newkirk, M M; Rioux, J D

    1995-09-01

    The human antibody response to foreign pathogens is generated to a relatively small number of target surface proteins and carbohydrates that nonetheless have an extensive array of epitopes. The study of human monoclonal antibodies to different pathogens shows that there are a diversity of mechanisms used to generate a sufficient repertoire of antibodies to combat the invading pathogens. Although many different immunoglobulin gene elements are used to construct the anti-pathogen response, some elements are used more often than would be expected if all elements were used randomly. For example, the immune response to Haemophilus influenzae polysaccharide appears to be quite narrow, being restricted primarily to a specific heavy-chain gene, 3-15, and a lambda light-chain family II member, 4A. In contrast, for the immune response to cytomegalovirus proteins, a wider group of gene elements is needed. It is also surprising that despite an investigator bias for IgG- rather than IgM-secreting immortal B cells (because of their high affinity and neutralizing abilities), 26% of light chains and 13% of heavy chains showed a very low level of somatic mutation, equivalent to an IgM molecule that has not undergone affinity maturation. Although some highly mutated IgG molecules are present in the anti-pathogen response, most of the monoclonal antibodies specific for viruses or bacteria have a level of somatic hypermutation similar to that of the adult IgM repertoire. A number of studies have shown that there are similarities in the antibody responses to pathogens and to self (autoantibodies).(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Gm typing by immunoglobulin heavy-chain gene RFLP analysis.

    OpenAIRE

    Jazwinska, E C; Dunckley, H; Propert, D N; Gatenby, P A; Serjeantson, S W

    1988-01-01

    This study was undertaken to investigate a means of assigning Gm allotypes to Caucasians by RFLP analysis. A single immunoglobulin heavy-chain gamma-4 cDNA probe (HU gamma 4) was hybridized with genomic DNA digested separately with two restriction enzymes, TaqI and PvuII. Results showed excellent correlation (P less than .001) between serologically defined Gm allotypes G1m(1), G1m(2), G2m(23), and G1m;G3m (3;5,10) and RFLPs identified with the (HU gamma 4) probe. We conclude that it is now po...

  7. Signals sustaining human immunoglobulin V gene hypermutation in isolated germinal centre B cells

    NARCIS (Netherlands)

    K. Dahlenborg; J.D. Pound (J.); J. Gordon (Jocelynne); C.A.K. Borrebaeck (C. A K); R. Carlsson (R.)

    2000-01-01

    textabstractAffinity maturation of antibody responses depends on somatic hypermutation of the immunoglobulin V genes. Hypermutation is initiated specifically in proliferating B cells in lymphoid germinal centres but the signals driving this process remain unknown. This study identifies signals that

  8. Biased Immunoglobulin Light Chain Gene Usage in the Shark.

    Science.gov (United States)

    Iacoangeli, Anna; Lui, Anita; Naik, Ushma; Ohta, Yuko; Flajnik, Martin; Hsu, Ellen

    2015-10-15

    This study of a large family of κ L chain clusters in nurse shark completes the characterization of its classical Ig gene content (two H chain isotypes, μ and ω, and four L chain isotypes, κ, λ, σ, and σ-2). The shark κ clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over an ~500-bp interval, and functional clusters are widely separated by at least 100 kb. Six out of ~39 κ clusters are prerearranged in the germline (germline joined). Unlike the complex gene organization and multistep assembly process of Ig in mammals, each shark Ig rearrangement, somatic or in the germline, appears to be an independent event localized to the minigene. This study examined the expression of functional, nonproductive, and sterile transcripts of the κ clusters compared with the other three L chain isotypes. κ cluster usage was investigated in young sharks, and a skewed pattern of split gene expression was observed, one similar in functional and nonproductive rearrangements. These results show that the individual activation of the spatially distant κ clusters is nonrandom. Although both split and germline-joined κ genes are expressed, the latter are prominent in young animals and wane with age. We speculate that, in the shark, the differential activation of the multiple isotypes can be advantageously used in receptor editing. Copyright © 2015 by The American Association of Immunologists, Inc.

  9. Immunoglobulin gene expression and regulation of rearrangement in kappa transgenic mice

    International Nuclear Information System (INIS)

    Ritchie, K.A.

    1986-01-01

    Transgenic mice were produced by microinjection of the functionally rearranged immunoglobulin kappa gene from the myeloma MOPC-21 into the male pronucleus of fertilized mouse eggs, and implantation of the microinjected embryos into foster mothers. Mice that integrated the injected gene were detected by hybridizing tail DNA dots with radioactively labelled pBR322 plasmid DNA, which detects pBR322 sequences left as a tag on the microinjected DNA. Mice that integrated the injected gene (six males) were mated and the DNA, RNA and serum kappa chains of their offspring were analyzed. A rabbit anti-mouse kappa chain antiserum was also produced for use in detection of mouse kappa chains on protein blots. Hybridomas were produced from the spleen cells of these kappa transgenic mice to immortalize representative B cells and to investigate expression of the transgenic kappa gene, its effect on allelic exclusion, and its effect on the control of light chain gene rearrangement and expression. The results show that the microinjected DNA is integrated as concatamers in unique single or, rarely, two separate sites in the genome. The concatamers are composed of several copies (16 to 64) of injected DNA arranged in a head to tail fashion. The transgene is expressed into protein normally and in a tissue specific fashion. For the first time in these transgenic mice, all tissues contain a functionally rearranged and potentially expressible immunoglobulin gene. The transgene is expressed only in B cells and not in hepatocytes, for example. This indicates that rearrangement of immunoglobulin genes is necessary but not sufficient for the tissue specific expression of these genes by B cells

  10. A Killer Immunoglobulin - Like Receptor Gene - Content Haplotype and A Cognate Human Leukocyte Antigen Ligand are Associated with Autism

    OpenAIRE

    Torres, Anthony; Westover, Jonna; Benson, Michael; Johnson, Randall; Dykes, Annelise

    2016-01-01

    The killing activity of natural killer cells is largely regulated by the binding of class I human leukocyte antigen cognate ligands to killer cell immunoglobulin - like receptor proteins. The killer cell immunoglobulin - like receptor gene - complex contains genes that activate and others that inhibit the killing state of natural killer cells depending on the binding of specific human leukocyte antigen cognate ligands. It has been suggested in previous publications that activating human leuko...

  11. Genetic stability of gene targeted immunoglobulin loci. I. Heavy chain isotype exchange induced by a universal gene replacement vector.

    Science.gov (United States)

    Kardinal, C; Selmayr, M; Mocikat, R

    1996-11-01

    Gene targeting at the immunoglobulin loci of B cells is an efficient tool for studying immunoglobulin expression or generating chimeric antibodies. We have shown that vector integration induced by human immunoglobulin G1 (IgG1) insertion vectors results in subsequent vector excision mediated by the duplicated target sequence, whereas replacement events which could be induced by the same constructs remain stable. We could demonstrate that the distribution of the vector homology strongly influences the genetic stability obtained. To this end we developed a novel type of a heavy chain replacement vector making use of the heavy chain class switch recombination sequence. Despite the presence of a two-sided homology this construct is universally applicable irrespective of the constant gene region utilized by the B cell. In comparison to an integration vector the frequency of stable incorporation was strongly increased, but we still observed vector excision, although at a markedly reduced rate. The latter events even occurred with circular constructs. Linearization of the construct at various sites and the comparison with an integration vector that carries the identical homology sequence, but differs in the distribution of homology, revealed the following features of homologous recombination of immunoglobulin genes: (i) the integration frequency is only determined by the length of the homology flank where the cross-over takes place; (ii) a 5' flank that does not meet the minimum requirement of homology length cannot be complemented by a sufficient 3' flank; (iii) free vector ends play a role for integration as well as for replacement targeting; (iv) truncating recombination events are suppressed in the presence of two flanks. Furthermore, we show that the switch region that was used as 3' flank is non-functional in an inverted orientation.

  12. Hypermutation in shark immunoglobulin light chain genes results in contiguous substitutions.

    Science.gov (United States)

    Lee, Susan S; Tranchina, Daniel; Ohta, Yuko; Flajnik, Martin F; Hsu, Ellen

    2002-04-01

    Among 631 substitutions present in 90 nurse shark immunoglobulin light chain somatic mutants, 338 constitute 2-4 bp stretches of adjacent changes. An absence of mutations in perinatal sequences and the bias for one mutating V gene in adults suggest that the diversification is antigen dependent. The substitutions shared no patterns, and the absence of donor sequences, including from family members, supports the idea that most changes arose from nontemplated mutation. The tandem mutations as a group are distinguished by consistently fewer transition changes and an A bias. We suggest this is one of several pathways of hypermutation diversifying shark antigen-receptor genes--point mutations, tandem mutations, and mutations with a G-C preference--that coevolved with or preceded gene rearrangement.

  13. Diversity of immunoglobulin lambda light chain gene usage over developmental stages in the horse.

    Science.gov (United States)

    Tallmadge, Rebecca L; Tseng, Chia T; Felippe, M Julia B

    2014-10-01

    To further studies of neonatal immune responses to pathogens and vaccination, we investigated the dynamics of B lymphocyte development and immunoglobulin (Ig) gene diversity. Previously we demonstrated that equine fetal Ig VDJ sequences exhibit combinatorial and junctional diversity levels comparable to those of adult Ig VDJ sequences. Herein, RACE clones from fetal, neonatal, foal, and adult lymphoid tissue were assessed for Ig lambda light chain combinatorial, junctional, and sequence diversity. Remarkably, more lambda variable genes (IGLV) were used during fetal life than later stages and IGLV gene usage differed significantly with time, in contrast to the Ig heavy chain. Junctional diversity measured by CDR3L length was constant over time. Comparison of Ig lambda transcripts to germline revealed significant increases in nucleotide diversity over time, even during fetal life. These results suggest that the Ig lambda light chain provides an additional dimension of diversity to the equine Ig repertoire. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Diagnostic value of immunoglobulin κ light chain gene rearrangement analysis in B-cell lymphomas.

    Science.gov (United States)

    Kokovic, Ira; Jezersek Novakovic, Barbara; Novakovic, Srdjan

    2015-03-01

    Analysis of the immunoglobulin κ light chain (IGK) gene is an alternative method for B-cell clonality assessment in the diagnosis of mature B-cell proliferations in which the detection of clonal immunoglobulin heavy chain (IGH) gene rearrangements fails. The aim of the present study was to evaluate the added value of standardized BIOMED-2 assay for the detection of clonal IGK gene rearrangements in the diagnostic setting of suspected B-cell lymphomas. With this purpose, 92 specimens from 80 patients with the final diagnosis of mature B-cell lymphoma (37 specimens), mature T-cell lymphoma (26 specimens) and reactive lymphoid proliferation (29 specimens) were analyzed for B-cell clonality. B-cell clonality analysis was performed using the BIOMED-2 IGH and IGK gene clonality assays. The determined sensitivity of the IGK assay was 67.6%, while the determined sensitivity of the IGH assay was 75.7%. The sensitivity of combined IGH+IGK assay was 81.1%. The determined specificity of the IGK assay was 96.2% in the group of T-cell lymphomas and 96.6% in the group of reactive lesions. The determined specificity of the IGH assay was 84.6% in the group of lymphomas and 86.2% in the group of reactive lesions. The comparison of GeneScan (GS) and heteroduplex pretreatment-polyacrylamide gel electrophoresis (HD-PAGE) methods for the analysis of IGK gene rearrangements showed a higher efficacy of GS analysis in a series of 27 B-cell lymphomas analyzed by both methods. In the present study, we demonstrated that by applying the combined IGH+IGK clonality assay the overall detection rate of B-cell clonality was increased by 5.4%. Thus, we confirmed the added value of the standardized BIOMED-2 IGK assay for assessment of B-cell clonality in suspected B-cell lymphomas with inconclusive clinical and cyto/histological diagnosis.

  15. Sequences of the joining region genes for immunoglobulin heavy chains and their role in generation of antibody diversity.

    OpenAIRE

    Gough, N M; Bernard, O

    1981-01-01

    To assess the contribution to immunoglobulin heavy chain diversity made by recombination between variable region (VH) genes and joining region (JH) genes, we have determined the sequence of about 2000 nucleotides spanning the rearranged JH gene cluster associated with the VH gene expressed in plasmacytoma HPC76. The active VH76 gene has recombined with the second germ-line JH gene. The region we have studied contains two other JH genes, designated JH3 and JH4. No other JH gene was found withi...

  16. Aberrant immunoglobulin and c-myc gene rearrangements in patients with nonmalignant monoclonal cryoglobulinemia

    International Nuclear Information System (INIS)

    Perl, A.; Wang, N.; Williams, J.M.; Hunt, M.J.; Rosenfeld, S.I.; Condemi, J.J.; Packman, C.H.; Abraham, G.N.

    1987-01-01

    The status of the immunoglobulin (Ig) genes was investigated in patients with idiopathic nonmalignant monoclonal IgG cryoglobulinemia (NCG). In NCG, monoclonal antibodies are synthesized at an accelerated rate by nonmalignant B lymphocytes. In order to determine whether this high production rate is related to a clonal B cell expansion, the rearrangement of the Ig genes was investigated by Southern blot analysis of genomic, 32 P-labelled, DNA extracted from the peripheral blood lymphocytes of four NCG patients. In three of four (VI, BR, and CH) clonal expansion of B cells was detected using probes specific for the genes. BamHI digestion of DNA from VI and BR produced three rearranged fragments which cohybridized with two of the probes. This finding suggested the presence of additional nonsecretory B cell clones and/or disruption of the gene segments spanned by and detected with the probes. In addition, the possibility of aberrant gene rearrangements was supported by noting the alteration of the c-myc gene locus in genomic DNA from peripheral blood leukocytes of VI and CH. Northern blot analysis of RNA isolated from peripheral blood B cells of VI and CH demonstrated aberrant transcripts of the c-myc gene, showing an active role of the altered c-myc locus. Detection of c-myc rearrangement in NCG patients clearly shows that this event may not be a final step in malignant B cell transformation

  17. Efficient immunoglobulin gene disruption and targeted replacement in rabbit using zinc finger nucleases.

    Directory of Open Access Journals (Sweden)

    Tatiana Flisikowska

    Full Text Available Rabbits are widely used in biomedical research, yet techniques for their precise genetic modification are lacking. We demonstrate that zinc finger nucleases (ZFNs introduced into fertilized oocytes can inactivate a chosen gene by mutagenesis and also mediate precise homologous recombination with a DNA gene-targeting vector to achieve the first gene knockout and targeted sequence replacement in rabbits. Two ZFN pairs were designed that target the rabbit immunoglobulin M (IgM locus within exons 1 and 2. ZFN mRNAs were microinjected into pronuclear stage fertilized oocytes. Founder animals carrying distinct mutated IgM alleles were identified and bred to produce offspring. Functional knockout of the immunoglobulin heavy chain locus was confirmed by serum IgM and IgG deficiency and lack of IgM(+ and IgG(+ B lymphocytes. We then tested whether ZFN expression would enable efficient targeted sequence replacement in rabbit oocytes. ZFN mRNA was co-injected with a linear DNA vector designed to replace exon 1 of the IgM locus with ∼1.9 kb of novel sequence. Double strand break induced targeted replacement occurred in up to 17% of embryos and in 18% of fetuses analyzed. Two major goals have been achieved. First, inactivation of the endogenous IgM locus, which is an essential step for the production of therapeutic human polyclonal antibodies in the rabbit. Second, establishing efficient targeted gene manipulation and homologous recombination in a refractory animal species. ZFN mediated genetic engineering in the rabbit and other mammals opens new avenues of experimentation in immunology and many other research fields.

  18. Immunoglobulin gene repertoire diversification and selection in the stomach – from gastritis to gastric lymphomas

    Directory of Open Access Journals (Sweden)

    Miri eMichaeli

    2014-06-01

    Full Text Available Chronic gastritis is characterized by gastric mucosal inflammation due to autoimmune responses or infection, frequently with Helicobacter pylori. Gastritis with H. pylori background can cause gastric mucosa-associated lymphoid tissue lymphoma (MALT-L, which sometimes further transforms into diffuse large B cell lymphoma (DLBCL. However, gastric DLBCL can also be initiated de novo. The mechanisms underlying transformation into DLBCL are not completely understood. We analyzed immunoglobulin repertoires and clonal trees to investigate whether and how immunoglobulin gene repertoires, clonal diversification and selection in gastritis, gastric MALT-L and DLBCL differ from each other and from normal responses. The two gastritis types (positive or negative for H. pylori had similarly diverse repertoires. MALT-L dominant clones presented higher diversification and longer mutational histories compared with all other conditions. DLBCL dominant clones displayed lower clonal diversification, suggesting the transforming events are triggered by similar responses in different patients. These results are surprising, as we expected to find similarities between the dominant clones of gastritis and MALT-L and between those of MALT-L and DLBCL.

  19. Nucleotide sequences of immunoglobulin eta genes of chimpanzee and orangutan: DNA molecular clock and hominoid evolution

    Energy Technology Data Exchange (ETDEWEB)

    Sakoyama, Y.; Hong, K.J.; Byun, S.M.; Hisajima, H.; Ueda, S.; Yaoita, Y.; Hayashida, H.; Miyata, T.; Honjo, T.

    1987-02-01

    To determine the phylogenetic relationships among hominoids and the dates of their divergence, the complete nucleotide sequences of the constant region of the immunoglobulin eta-chain (C/sub eta1/) genes from chimpanzee and orangutan have been determined. These sequences were compared with the human eta-chain constant-region sequence. A molecular clock (silent molecular clock), measured by the degree of sequence divergence at the synonymous (silent) positions of protein-encoding regions, was introduced for the present study. From the comparison of nucleotide sequences of ..cap alpha../sub 1/-antitrypsin and ..beta..- and delta-globulin genes between humans and Old World monkeys, the silent molecular clock was calibrated: the mean evolutionary rate of silent substitution was determined to be 1.56 x 10/sup -9/ substitutions per site per year. Using the silent molecular clock, the mean divergence dates of chimpanzee and orangutan from the human lineage were estimated as 6.4 +/- 2.6 million years and 17.3 +/- 4.5 million years, respectively. It was also shown that the evolutionary rate of primate genes is considerably slower than those of other mammalian genes.

  20. Mapping the transcription termination region of the mouse immunoglobulin kappa gene

    International Nuclear Information System (INIS)

    Xu, M.; Garrard, W.T.

    1986-01-01

    To define the transcription termination region of the mouse immunoglobulin kappa gene, they have subcloned single copy DNA sequences corresponding to both the template and the non-template strands of this locus. In vitro nuclear transcription with isolated MPC-11 nuclei was performed and the resulting 32 P-labeled RNA was hybridized to slot-blotted, single-stranded M13 probes covering regions within and flanking the kappa gene. The hybridization pattern for the template-strand reveals that transcription terminates within the region between 1.1 to 2.3 kb downstream from the poly(A) site. Ten different short sequences (8-13 bp) reside within 460 bp of this region that exhibit homology with sequences found in the termination regions of mouse β-globin and chicken ovalbumin genes. Transcription of the non-template strand occurs on either side of this termination region. They note that no transcription is detectable on the non-template strand downstream of the enhancer, indicating that if RNA polymerase II enters at this site, it does not initiate transcription during transit to the promoter region. They conclude that transcription of the kappa gene passes the poly(A) addition site and terminates within 2.3 Kb downstream

  1. Killer cell immunoglobulin-like receptor gene diversity in the Tibetan ethnic minority group of China.

    Science.gov (United States)

    Zhu, Bo-feng; Wang, Hong-dan; Shen, Chun-mei; Deng, Ya-jun; Yang, Guang; Wu, Qing-ju; Xu, Peng; Qin, Hai-xia; Fan, Shuan-liang; Huang, Ping; Deng, Li-bin; Lucas, Rudolf; Wang, Zhen-Yuan

    2010-11-01

    The aim of this study was to analyze killer immunoglobulin-like receptor (KIR) gene polymorphisms in the Tibetan ethnic minority of China. To that purpose, we have studied KIR gene frequencies and genotype diversities of 16 KIR genes and three pseudogenes (2DL1, 2DL2, 2DL3, 2DL4, 2DL5A, 2DL5B, 2DS1, 2DS2, 2DS3, 2DS4*001/002, 2DS4*003-007, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1, 2DP1, 3DP1*001/002/004, and 3DP1*003) in a population sample of 102 unrelated healthy individuals of the Tibetan population living in Lhasa city, Tibet Autonomous Region of China. Tibetans mainly live in "the roof of the world," the Qinghai-Tibet Plateau of China and surrounding areas stretching from central Asia in the North and West to Myanmar and mainland China in the East, and India, Nepal, and Bhutan to the south. KIR gene frequencies and statistical parameters of Tibetan ethnic minority were calculated. Fifteen KIR genes were observed in the 102 tested Tibetan individuals with different frequencies. The allelic frequencies of the 15 KIR genes ranged from 0.06 to 0.86. In addition, KIR 2DL1, 2DL4, 3DL2, and 3DL3 were found to be present in every individual. Variable gene content, together with allelic polymorphisms, can result in individualized human KIR genotypes and haplotypes, with the A haplotypes being predominantly observed. The results of tested linkage disequilibrium (LD) among KIR genes demonstrated that KIR genes present a wide range of linkage disequilibrium. Moreover, a comparison of the population data of our study with previously published population data of other ethnic groups or areas was performed. The differences of allelic frequency distribution in KIR2DL2, 2DL3, 2DL5, 3DL1, 2DS1, 2DS2, 2DS3, 3DS1, and 2DP1 were statistically significant among different populations using the statistical method of the standard χ(2) test. In conclusion, the results of the present study can be valuable for enriching the Chinese ethnical gene information resources of the KIR gene pool and for

  2. Fish Immunoglobulins

    OpenAIRE

    Sara Mashoof; Michael F. Criscitiello

    2016-01-01

    The B cell receptor and secreted antibody are at the nexus of humoral adaptive immunity. In this review, we summarize what is known of the immunoglobulin genes of jawed cartilaginous and bony fishes. We focus on what has been learned from genomic or cDNA sequence data, but where appropriate draw upon protein, immunization, affinity and structural studies. Work from major aquatic model organisms and less studied comparative species are both included to define what is the rule for an immunoglob...

  3. Automated cleaning and pre-processing of immunoglobulin gene sequences from high-throughput sequencing

    Directory of Open Access Journals (Sweden)

    Miri eMichaeli

    2012-12-01

    Full Text Available High throughput sequencing (HTS yields tens of thousands to millions of sequences that require a large amount of pre-processing work to clean various artifacts. Such cleaning cannot be performed manually. Existing programs are not suitable for immunoglobulin (Ig genes, which are variable and often highly mutated. This paper describes Ig-HTS-Cleaner (Ig High Throughput Sequencing Cleaner, a program containing a simple cleaning procedure that successfully deals with pre-processing of Ig sequences derived from HTS, and Ig-Indel-Identifier (Ig Insertion – Deletion Identifier, a program for identifying legitimate and artifact insertions and/or deletions (indels. Our programs were designed for analyzing Ig gene sequences obtained by 454 sequencing, but they are applicable to all types of sequences and sequencing platforms. Ig-HTS-Cleaner and Ig-Indel-Identifier have been implemented in Java and saved as executable JAR files, supported on Linux and MS Windows. No special requirements are needed in order to run the programs, except for correctly constructing the input files as explained in the text. The programs' performance has been tested and validated on real and simulated data sets.

  4. Immunoglobulin GM and KM genes and measles vaccine-induced humoral immunity.

    Science.gov (United States)

    Ovsyannikova, Inna G; Larrabee, Beth R; Schaid, Daniel J; Poland, Gregory A

    2017-10-04

    Identifying genetic polymorphisms that explain variations in humoral immunity to live measles virus vaccine is of great interest. Immunoglobulin GM (heavy chain) and KM (light chain) allotypes are genetic markers known to be associated with susceptibility to several infectious diseases. We assessed associations between GM and KM genotypes and measles vaccine humoral immunity (neutralizing antibody titers) in a combined cohort (n=1796) of racially diverse healthy individuals (age 18-41years). We did not discover any significant associations between GM and/or KM genotypes and measles vaccine-induced neutralizing antibody titers. African-American subjects had higher neutralizing antibody titers than Caucasians (1260mIU/mL vs. 740mIU/mL, p=7.10×10 -13 ), and those titers remained statistically significant (p=1.68×10 -09 ) after adjusting for age at enrollment and time since last vaccination. There were no statistically significant sex-specific differences in measles-induced neutralizing antibody titers in our study (p=0.375). Our data indicate a surprising lack of evidence for an association between GM and KM genotypes and measles-specific neutralizing antibody titers, despite the importance of these immune response genes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Molecular analysis of immunoglobulin genes reveals frequent clonal relatedness in double monoclonal gammopathies.

    Science.gov (United States)

    Tschumper, R C; Dispenzieri, A; Abraham, R S; Henderson, K J; Jelinek, D F

    2013-04-19

    Monoclonal gammopathies (MGs) are hematological diseases characterized by high levels of a monoclonal immunoglobulin (Ig) or M-protein. Within this group are patients with more than one M-protein, referred to as double MGs (DMGs). The M-proteins in DMG patients may have different heavy chain (HC) isotypes that are associated with different light chains (LCs), or different HCs that are LC matched. In this study, we examined the clonal relatedness of the M-proteins in the latter type in a cohort of 14 DMG patients. By using PCR, we identified 7/14 DMG patients that expressed two Ig HC isotypes with identical Ig HC variable (IGHV), diversity (IGHD), joining (IGHJ), and complementarity determining region (HCDR3) sequences. Two additional DMG patients had two Ig transcripts using the same IGHV, IGHD and IGHJ genes but with slight differences in variable region or HCDR3 mutations. LC analysis confirmed that a single LC was expressed in 3/7 DMG patients with identical HC transcripts and in the two DMGs with highly similar transcripts. The PCR findings were confirmed by immunofluorescence for HC and LC expression. Clonally related HC-dissimilar/LC-matched DMGs may occur often and defines a new subtype of MG that may serve as a tool for studies of disease pathogenesis.

  6. Molecular analysis of immunoglobulin genes reveals frequent clonal relatedness in double monoclonal gammopathies

    International Nuclear Information System (INIS)

    Tschumper, R C; Dispenzieri, A; Abraham, R S; Henderson, K J; Jelinek, D F

    2013-01-01

    Monoclonal gammopathies (MGs) are hematological diseases characterized by high levels of a monoclonal immunoglobulin (Ig) or M-protein. Within this group are patients with more than one M-protein, referred to as double MGs (DMGs). The M-proteins in DMG patients may have different heavy chain (HC) isotypes that are associated with different light chains (LCs), or different HCs that are LC matched. In this study, we examined the clonal relatedness of the M-proteins in the latter type in a cohort of 14 DMG patients. By using PCR, we identified 7/14 DMG patients that expressed two Ig HC isotypes with identical Ig HC variable (IGHV), diversity (IGHD), joining (IGHJ), and complementarity determining region (HCDR3) sequences. Two additional DMG patients had two Ig transcripts using the same IGHV, IGHD and IGHJ genes but with slight differences in variable region or HCDR3 mutations. LC analysis confirmed that a single LC was expressed in 3/7 DMG patients with identical HC transcripts and in the two DMGs with highly similar transcripts. The PCR findings were confirmed by immunofluorescence for HC and LC expression. Clonally related HC-dissimilar/LC-matched DMGs may occur often and defines a new subtype of MG that may serve as a tool for studies of disease pathogenesis

  7. Diversity analysis of the immunoglobulin M heavy chain gene in Nile ...

    African Journals Online (AJOL)

    nu tom

    2015-07-22

    Jul 22, 2015 ... related industries and supply chains, such as hatcheries, feed manufacturers ... system has a high risk of disease outbreaks. The bulk of ...... immunoglobulin heavy-chain locus in zebrafish: identification and expression of a ...

  8. Detection of clonal immunoglobulin heavy chain gene rearrangements by the polymerase chain reaction and capillary gel electrophoresis.

    Science.gov (United States)

    Fan, Hongxin; Robetorye, Ryan S

    2013-01-01

    Although well-established diagnostic criteria exist for mature B-cell neoplasms, a definitive diagnosis of a B-cell lymphoproliferative disorder cannot always be obtained using more conventional techniques such as flow cytometric immunophenotyping, conventional cytogenetics, fluorescence in situ hybridization, or immunohistochemistry. However, because B-cell malignancies contain identically rearranged immunoglobulin heavy chain genes, the polymerase chain reaction (PCR) can be a fast, convenient, and dependable option to identify clonal B-cell processes. This chapter describes the use of PCR and capillary electrophoresis to identify clonal immunoglobulin heavy chain (IGH) variable and joining region (VH-JH) gene rearrangements (IGH VH-JH PCR) using a commercially available method employing multiple multiplex PCR tubes that was originally developed as the result of a large European BIOMED-2 collaborative study (Invivoscribe Technologies). The core protocol involves the use of three separate master mix tubes that target the conserved framework (FR1, FR2, and FR3) and joining (J) regions of the IGH gene. Analysis of these three framework regions can detect approximately 88% of clonal IGH gene rearrangements.

  9. A conserved gene family encodes transmembrane proteins with fibronectin, immunoglobulin and leucine-rich repeat domains (FIGLER

    Directory of Open Access Journals (Sweden)

    Haga Christopher L

    2007-09-01

    Full Text Available Abstract Background In mouse the cytokine interleukin-7 (IL-7 is required for generation of B lymphocytes, but human IL-7 does not appear to have this function. A bioinformatics approach was therefore used to identify IL-7 receptor related genes in the hope of identifying the elusive human cytokine. Results Our database search identified a family of nine gene candidates, which we have provisionally named fibronectin immunoglobulin leucine-rich repeat (FIGLER. The FIGLER 1–9 genes are predicted to encode type I transmembrane glycoproteins with 6–12 leucine-rich repeats (LRR, a C2 type Ig domain, a fibronectin type III domain, a hydrophobic transmembrane domain, and a cytoplasmic domain containing one to four tyrosine residues. Members of this multichromosomal gene family possess 20–47% overall amino acid identity and are differentially expressed in cell lines and primary hematopoietic lineage cells. Genes for FIGLER homologs were identified in macaque, orangutan, chimpanzee, mouse, rat, dog, chicken, toad, and puffer fish databases. The non-human FIGLER homologs share 38–99% overall amino acid identity with their human counterpart. Conclusion The extracellular domain structure and absence of recognizable cytoplasmic signaling motifs in members of the highly conserved FIGLER gene family suggest a trophic or cell adhesion function for these molecules.

  10. Similarities in the immunoglobulin response and VH gene usage in rhesus monkeys and humans exposed to porcine hepatocytes

    Directory of Open Access Journals (Sweden)

    Borie Dominic C

    2006-03-01

    Full Text Available Abstract Background The use of porcine cells and organs as a source of xenografts for human patients would vastly increase the donor pool; however, both humans and Old World primates vigorously reject pig tissues due to xenoantibodies that react with the polysaccharide galactose α (1,3 galactose (αGal present on the surface of many porcine cells. We previously examined the xenoantibody response in patients exposed to porcine hepatocytes via treatment(s with bioartficial liver devices (BALs, composed of porcine cells in a support matrix. We determined that xenoantibodies in BAL-treated patients are predominantly directed at porcine αGal carbohydrate epitopes, and are encoded by a small number of germline heavy chain variable region (VH immunoglobulin genes. The studies described in this manuscript were designed to identify whether the xenoantibody responses and the IgVH genes encoding antibodies to porcine hepatocytes in non-human primates used as preclinical models are similar to those in humans. Adult non-immunosuppressed rhesus monkeys (Macaca mulatta were injected intra-portally with porcine hepatocytes or heterotopically transplanted with a porcine liver lobe. Peripheral blood leukocytes and serum were obtained prior to and at multiple time points after exposure, and the immune response was characterized, using ELISA to evaluate the levels and specificities of circulating xenoantibodies, and the production of cDNA libraries to determine the genes used by B cells to encode those antibodies. Results Xenoantibodies produced following exposure to isolated hepatocytes and solid organ liver grafts were predominantly encoded by genes in the VH3 family, with a minor contribution from the VH4 family. Immunoglobulin heavy-chain gene (VH cDNA library screening and gene sequencing of IgM libraries identified the genes as most closely-related to the IGHV3-11 and IGHV4-59 germline progenitors. One of the genes most similar to IGHV3-11, VH3-11cyno, has

  11. Expression of members of immunoglobulin gene family in somatic cell hybrids between human B and T cells

    International Nuclear Information System (INIS)

    Kozbor, D.; Burioni, R.; Ar-Rushdi, A.; Zmijewski, C.; Croce, C.M.

    1987-01-01

    Somatic cell hybrids were obtained between human T and B cells and tested for the expression of differentiated traits of both cell lineages. The T-cell parent SUP-T1 is CD3 - , CD4 + , CD1 + , CD8 + , is weakly positive for HLA class I determinants, and has an inversion of chromosome 14 due to a site-specific recombination event between an immunoglobulin heavy-chain variable gene and the joining segment of the T-cell receptor α chain. The B-cell parent, the 6-thioguanine- and ouabain-resistant mutant GM1500, is a lymphoblastoid cell line that secretes IgG2, K chains, and expresses B1, B532, and HLA class I and II antigens. All hybrids expressed characteristics of B cells (Ig + , B1 + , B532 + , EBNA + , HLA antigens), whereas only CD4 among the T-cell markers was expressed. The level of T-cell receptor β-chain transcript was greatly reduced and no RNA of the chimeric T-cell receptor α-chain joining segment-immunoglobulin heavy-chain variable region was detected. Southern blot analysis indicated that absence of T-cell differentiation markers in the hybrids was not due to chromosomal loss. Rather, some B-cell-specific factor present in the hybrids may account for the suppression

  12. KILLER CELL IMMUNOGLOBULIN-LIKE RECEPTOR GENES AND THEIR HLA-C LIGANDS IN HASHIMOTO THYROIDITIS IN A CHINESE POPULATION.

    Science.gov (United States)

    Li, Jian-Ting; Guo, Cheng; Li, Ming-Long; Wei, Yong-Qing; Hou, Yan-Feng; Jiao, Yu-Lian; Zhao, Yue-Ran; Sun, Hui; Xu, Jin; Cao, Ming-Feng; Feng, Li; Yu, Gui-Na; Gao, Ling; Liu, Yi-Qing; Zhang, Bing-Chang; Zhao, Jia-Jun; Zhang, Hai-Qing

    2016-08-01

    Natural killer (NK) cells serve as primary immune surveillance and are partially regulated by combinations of killer immunoglobulin-like receptors (KIR) and their human leukocyte antigen-C (HLA-C) ligands. Alterations in NK cell activity have been associated with Hashimoto thyroiditis (HT). The aim of this study was to determine whether certain KIR/HLA-C genotype combinations play a role in HT pathogenesis. The present study enrolled 107 unrelated HT patients and 108 random healthy individuals in a case-control study. Blood was collected for DNA extraction; typing of KIR genes and HLA-C alleles was performed by polymerase chain reaction with sequence specific primers (PCR-SSP), followed by electrophoresis on agarose gels. Among a panel of KIR2D/HLA-C genotype combinations, the frequency of KIR2DS2/HLA-C1 was significantly increased in HT patients compared to controls (33.64% vs. 12.96%, PHashimoto thyroiditis KIR = killer immunoglobulin-like receptor NK = natural killer PCR = polymerase chain reaction.

  13. The short mRNA isoform of the immunoglobulin superfamily, member 1 gene encodes an intracellular glycoprotein.

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    Ying Wang

    Full Text Available Mutations in the immunoglobulin superfamily, member 1 gene (IGSF1/Igsf1 cause an X-linked form of central hypothyroidism. The canonical form of IGSF1 is a transmembrane glycoprotein with 12 immunoglobulin (Ig loops. The protein is co-translationally cleaved into two sub-domains. The carboxyl-terminal domain (CTD, which contains the last 7 Ig loops, is trafficked to the plasma membrane. Most pathogenic mutations in IGSF1 map to the portion of the gene encoding the CTD. IGSF1/Igsf1 encodes a variety of transcripts. A little studied, but abundant splice variant encodes a truncated form of the protein, predicted to contain the first 2 Ig loops of the full-length IGSF1. The protein (hereafter referred to as IGSF1 isoform 2 or IGSF1-2 is likely retained in most individuals with IGSF1 mutations. Here, we characterized basic biochemical properties of the protein as a foray into understanding its potential function. IGSF1-2, like the IGSF1-CTD, is a glycoprotein. In both mouse and rat, the protein is N-glycosylated at a single asparagine residue in the first Ig loop. Contrary to earlier predictions, neither the murine nor rat IGSF1-2 is secreted from heterologous or homologous cells. In addition, neither protein associates with the plasma membrane. Rather, IGSF1-2 appears to be retained in the endoplasmic reticulum. Whether the protein plays intracellular functions or is trafficked through the secretory pathway under certain physiologic or pathophysiologic conditions has yet to be determined.

  14. Diversity of killer cell immunoglobulin-like receptor genes in the Bengali population of northern West Bengal, India.

    Science.gov (United States)

    Guha, P; Bhattacharjee, S; Chaudhuri, T K

    2014-12-01

    The Indian Subcontinent exhibits extensive diversity in its culture, religion, ethnicity and linguistic heritage, which symbolizes extensive genetic variations within the populations. The highly polymorphic Killer cell Immunoglobulin-like Receptor (KIR) family plays an important role in tracing genetic differentiation in human population. In this study, we aimed to analyse the KIR gene polymorphism in the Bengali population of northern West Bengal, India. To our knowledge, this is the first report on the KIR gene polymorphism in the Bengalis of West Bengal, India. Herein, we have studied the distribution of 14 KIR genes (KIR3DL1-3DL3, KIR2DL1-2DL5, KIR2DS1-2DS5 AND KIR3DS1) and two pseudogenes (KIR3DP1 and 2DP1) in the Bengalis. Apart from the framework genes (KIR2DL4, 3DL2, 3DL3 and 3DP1), which are present in all the individuals, the gene frequencies of other KIR genes varied between 0.34 and 0.88. Moreover, upon comparing the KIR polymorphism of the Bengalis with the available published data of other world populations, it has been found that the Indo-European-speaking Bengalis from the region share both Dravidian and Indo-Aryan gene pool with considerable influences of mongoloid and European descents. Furthermore, evidences from previously published data on human leucocyte antigen and Y-chromosome haplogroup diversity support the view. Our results will help to understand the genetic background of the Bengali population, in illustrating the population migration events in the eastern and north-eastern part of India, in explaining the extensive genetic admixture amongst the different linguistic groups of the region and also in KIR-related disease researches. © 2014 John Wiley & Sons Ltd.

  15. Upregulation of Immunoglobulin-related Genes in Cortical Sections from Multiple Sclerosis Patients

    NARCIS (Netherlands)

    Torkildsen, O.; Stansberg, C.; Angelskar, S.M.; Kooi, E.J.; Geurts, J.J.G.; van der Valk, P.; Myhr, K.M.; Steen, V.M.; Bo, L.

    2010-01-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). Microarray-based global gene expression profiling is a promising method, used to study potential genes involved in the pathogenesis of the disease. In the present study, we have examined global gene expression in

  16. PCR-based clonality analysis of B-cell lymphomas in paraffin-embedded tissues: diagnostic value of immunoglobulin kappa and lambda light chain gene rearrangement investigation.

    Science.gov (United States)

    Amara, Khaled; Trimeche, Mounir; Ziadi, Sonia; Sriha, Badreddine; Mokni, Moncef; Korbi, Sadok

    2006-01-01

    Polymerase chain reaction (PCR)-based analysis, employed for detecting immunoglobulin heavy chain (IgH) gene rearrangements, has become a diagnostic tool widely used in the investigation of B-cell lymphomas, but the overall sensitivity of these methods does not exceed 80%, notably in germinal center (GC) and post-GC B-cell origin lymphomas. Many PCR strategies devised for detecting immunoglobulin light chain (IgL) gene rearrangements have been developed to enhance the clonality detection rates. However, the feasibility of these methods in routine clinical diagnosis using paraffin-embedded tissues has not yet been investigated sufficiently. We studied a large series of 108 cases of B-cell lymphomas, as well as 20 reactive lymphoid tissues using degenerate primers to amplify immunoglobulin kappa (Igkappa) and lambda (Iglambda) light chain genes. B-cell clonality was further investigated using semi-nested PCR for IgH gene rearrangements. B-cell clonality was detected in 74%, 56.5%, and 43.5% of cases using IgH, Igkappa, and Iglambda PCR, respectively. By combining these methods, the clonality detection rate increased to 93.5%. Only polyclonal patterns were noted in reactive lymphoid samples. We concluded that in addition to the established methods for IgH analysis, a PCR-based approach for IgL gene rearrangements analysis improves the clonality detection rate in over 90% of B-cell lymphoma cases using routine histological specimens with poor preservation of the genomic DNA.

  17. Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes.

    Science.gov (United States)

    Macdonald, Lynn E; Karow, Margaret; Stevens, Sean; Auerbach, Wojtek; Poueymirou, William T; Yasenchak, Jason; Frendewey, David; Valenzuela, David M; Giallourakis, Cosmas C; Alt, Frederick W; Yancopoulos, George D; Murphy, Andrew J

    2014-04-08

    Genetic humanization, which involves replacing mouse genes with their human counterparts, can create powerful animal models for the study of human genes and diseases. One important example of genetic humanization involves mice humanized for their Ig genes, allowing for human antibody responses within a mouse background (HumAb mice) and also providing a valuable platform for the generation of fully human antibodies as therapeutics. However, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which they were genetically humanized. Heretofore, most genetic humanizations have involved disruption of the endogenous mouse gene with simultaneous introduction of a human transgene at a new and random location (so-called KO-plus-transgenic humanization). More recent efforts have attempted to replace mouse genes with their human counterparts at the same genetic location (in situ humanization), but such efforts involved laborious procedures and were limited in size and precision. We describe a general and efficient method for very large, in situ, and precise genetic humanization using large compound bacterial artificial chromosome-based targeting vectors introduced into mouse ES cells. We applied this method to genetically humanize 3-Mb segments of both the mouse heavy and κ light chain Ig loci, by far the largest genetic humanizations ever described. This paper provides a detailed description of our genetic humanization approach, and the companion paper reports that the humoral immune systems of mice bearing these genetically humanized loci function as efficiently as those of WT mice.

  18. Innate Functions of Immunoglobulin M Lessen Liver Gene Transfer with Helper-Dependent Adenovirus

    Science.gov (United States)

    Unzu, Carmen; Morales-Kastresana, Aizea; Sampedro, Ana; Serrano-Mendioroz, Irantzu; Azpilikueta, Arantza; Ochoa, María Carmen; Dubrot, Juan; Martínez-Ansó, Eduardo

    2014-01-01

    The immune system poses obstacles to viral vectors, even in the first administration to preimmunized hosts. We have observed that the livers of B cell-deficient mice were more effectively transduced by a helper-dependent adenovirus serotype-5 (HDA) vector than those of WT mice. This effect was T-cell independent as shown in athymic mice. Passive transfer of the serum from adenovirus-naïve WT to Rag1KO mice resulted in a reduction in gene transfer that was traced to IgM purified from serum of adenovirus-naïve mice. To ascribe the gene transfer inhibition activity to either adenoviral antigen-specific or antigen-unspecific functions of IgM, we used a monoclonal IgM antibody of unrelated specificity. Both the polyclonal and the irrelevant monoclonal IgM inhibited gene transfer by the HDA vector to either cultured hepatocellular carcinoma cells or to the liver of mice in vivo. Adsorption of polyclonal or monoclonal IgMs to viral capsids was revealed by ELISAs on adenovirus-coated plates. These observations indicate the existence of an inborn IgM mechanism deployed against a prevalent virus to reduce early post-infection viremia. In conclusion, innate IgM binding to adenovirus serotype-5 capsids restrains gene-transfer and offers a mechanism to be targeted for optimization of vector dosage in gene therapy with HDA vectors. PMID:24465560

  19. Innate functions of immunoglobulin M lessen liver gene transfer with helper-dependent adenovirus.

    Directory of Open Access Journals (Sweden)

    Carmen Unzu

    Full Text Available The immune system poses obstacles to viral vectors, even in the first administration to preimmunized hosts. We have observed that the livers of B cell-deficient mice were more effectively transduced by a helper-dependent adenovirus serotype-5 (HDA vector than those of WT mice. This effect was T-cell independent as shown in athymic mice. Passive transfer of the serum from adenovirus-naïve WT to Rag1KO mice resulted in a reduction in gene transfer that was traced to IgM purified from serum of adenovirus-naïve mice. To ascribe the gene transfer inhibition activity to either adenoviral antigen-specific or antigen-unspecific functions of IgM, we used a monoclonal IgM antibody of unrelated specificity. Both the polyclonal and the irrelevant monoclonal IgM inhibited gene transfer by the HDA vector to either cultured hepatocellular carcinoma cells or to the liver of mice in vivo. Adsorption of polyclonal or monoclonal IgMs to viral capsids was revealed by ELISAs on adenovirus-coated plates. These observations indicate the existence of an inborn IgM mechanism deployed against a prevalent virus to reduce early post-infection viremia. In conclusion, innate IgM binding to adenovirus serotype-5 capsids restrains gene-transfer and offers a mechanism to be targeted for optimization of vector dosage in gene therapy with HDA vectors.

  20. Major histocompatibility complex class III genes and susceptibility to immunoglobulin A deficiency and common variable immunodeficiency.

    OpenAIRE

    Volanakis, J E; Zhu, Z B; Schaffer, F M; Macon, K J; Palermos, J; Barger, B O; Go, R; Campbell, R D; Schroeder, H W; Cooper, M D

    1992-01-01

    We have proposed that significant subsets of individuals with IgA deficiency (IgA-D) and common variable immunodeficiency (CVID) may represent polar ends of a clinical spectrum reflecting a single underlying genetic defect. This proposal was supported by our finding that individuals with these immunodeficiencies have in common a high incidence of C4A gene deletions and C2 rare gene alleles. Here we present our analysis of the MHC haplotypes of 12 IgA-D and 19 CVID individuals from 21 families...

  1. Altered phenotypic expression of immunoglobulin heavy-chain variable-region (VH) genes in Alicia rabbits probably reflects a small deletion in the VH genes closest to the joining region.

    Science.gov (United States)

    Allegrucci, M; Newman, B A; Young-Cooper, G O; Alexander, C B; Meier, D; Kelus, A S; Mage, R G

    1990-07-01

    Rabbits of the Alicia strain have a mutation (ali) that segregates with the immunoglobulin heavy-chain (lgh) locus and has a cis effect upon the expression of heavy-chain variable-region (VH) genes encoding the a2 allotype. In heterozygous a1/ali or a3/ali rabbits, serum immunoglobulins are almost entirely the products of the normal a1 or a3 allele and only traces of a2 immunoglobulin are detectable. Adult homozygous ali/ali rabbits likewise have normal immunoglobulin levels resulting from increased production of a-negative immunoglobulins and some residual ability to produce the a2 allotype. By contrast, the majority of the immunoglobulins of wild-type a2 rabbits are a2-positive and only a small percentage are a-negative. Genomic DNAs from homozygous mutant and wild-type animals were indistinguishable by Southern analyses using a variety of restriction enzyme digests and lgh probes. However, when digests with infrequently cutting enzymes were analyzed by transverse alternating-field electrophoresis, the ali DNA fragments were 10-15 kilobases smaller than the wild type. These fragments hybridized to probes both for VH and for a region of DNA a few kilobases downstream of the VH genes nearest the joining region. We suggest that this relatively small deletion affects a segment containing 3' VH genes with important regulatory functions, the loss of which leads to the ali phenotype. These results, and the fact that the 3' VH genes rearrange early in B-cell development, indicate that the 3' end of the VH locus probably plays a key role in regulation of VH gene expression.

  2. Immunoglobulin genes and T-cell receptors as molecular markers in children with acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Lazić Jelena

    2009-01-01

    Full Text Available Introduction. Acute lymphoblastic leukaemia (ALL is a malignant clonal disease, one of the most common malignancies in childhood. Contemporary protocols ensure high remission rate and long term free survival. The ability of molecular genetic methods help to establish submicroscopic classification and minimal residual disease (MRD follow up, in major percent responsible for relapse. Objective. The aim of the study was to detect the frequency of IgH and TCR gene rearrangements and their correlation with clinical parameters. Methods. Forty-one children with ALL were enrolled in the study group, with initial diagnosis of IgH and TCR gene rearrangements by polimerase chain reaction ( PCR. MRD follow-up was performed in induction phase when morphological remission was expected, and after intensive chemiotherapy. Results. In the study group IgH rearrangement was detected in 82.9% of children at the diagnosis, while TCR rearrangement was seen in 56.1%. On induction day 33, clonal IgH rearrangements persisted in 39% and TCR rearrangements in 36.5% of children. Conclusion. Molecular analysis of genetic alterations and their correlation with standard prognostic parameters show the importance of risk stratification revision which leads to new therapy intensification approach. MRD stands out as a precise predictive factor for the relapse of disease.

  3. CIG-DB: the database for human or mouse immunoglobulin and T cell receptor genes available for cancer studies

    Directory of Open Access Journals (Sweden)

    Furue Motoki

    2010-07-01

    Full Text Available Abstract Background Immunoglobulin (IG or antibody and the T-cell receptor (TR are pivotal proteins in the immune system of higher organisms. In cancer immunotherapy, the immune responses mediated by tumor-epitope-binding IG or TR play important roles in anticancer effects. Although there are public databases specific for immunological genes, their contents have not been associated with clinical studies. Therefore, we developed an integrated database of IG/TR data reported in cancer studies (the Cancer-related Immunological Gene Database [CIG-DB]. Description This database is designed as a platform to explore public human and murine IG/TR genes sequenced in cancer studies. A total of 38,308 annotation entries for IG/TR proteins were collected from GenBank/DDBJ/EMBL and the Protein Data Bank, and 2,740 non-redundant corresponding MEDLINE references were appended. Next, we filtered the MEDLINE texts by MeSH terms, titles, and abstracts containing keywords related to cancer. After we performed a manual check, we classified the protein entries into two groups: 611 on cancer therapy (Group I and 1,470 on hematological tumors (Group II. Thus, a total of 2,081 cancer-related IG and TR entries were tabularized. To effectively classify future entries, we developed a computational method based on text mining and canonical discriminant analysis by parsing MeSH/title/abstract words. We performed a leave-one-out cross validation for the method, which showed high accuracy rates: 94.6% for IG references and 94.7% for TR references. We also collected 920 epitope sequences bound with IG/TR. The CIG-DB is equipped with search engines for amino acid sequences and MEDLINE references, sequence analysis tools, and a 3D viewer. This database is accessible without charge or registration at http://www.scchr-cigdb.jp/, and the search results are freely downloadable. Conclusions The CIG-DB serves as a bridge between immunological gene data and cancer studies, presenting

  4. Interaction of maternal atopy, CTLA-4 gene polymorphism and gender on antenatal immunoglobulin E production.

    Science.gov (United States)

    Yang, K D; Ou, C-Y; Hsu, T-Y; Chang, J-C; Chuang, H; Liu, C-A; Liang, H-M; Kuo, H-C; Chen, R-F; Huang, E-Y

    2007-05-01

    Genetic heritability and maternal atopy have been correlated to antenatal IgE production, but very few studies have studied gene-maternal atopy interaction on antenatal IgE production. This study investigated the interaction of CTLA-4 polymorphism with prenatal factors on the elevation of cord blood IgE (CBIgE). Pregnant women were antenatally recruited for collection of prenatal environmental factors by a questionnaire. Umbilical cord blood samples were collected for CBIgE detection by fluorescence-linked enzyme assay and CTLA-4 polymorphism measurement by restriction fragment length polymorphism. A total of 1104 pregnant women initially participated in this cohort study, and 898 of them completed cord blood collection. 21.4% of the newborns had elevation of CBIgE (>or=0.5 kU/L). The CTLA-4+49A allele (P=0.021), maternal atopy (Ppaternal atopy, were significantly correlated with the CBIgE elevation in multivariate analysis. A dichotomous analysis of gene-maternal atopy interactions identified maternal atopy and CTLA-4+49A allele had an additive effect on the CBIgE elevation, especially prominent in male newborns; and in the absence of maternal atopy, CTLA-4+49GG genotype had a protective effect on CBIgE elevation in female newborns. Maternal but not paternal atopy has significant impacts on CBIgE elevation depending on gender and CTLA-4+49A/G polymorphism of newborns. Control of maternal atopy and modulation of CTLA-4 expression in the prenatal stage may be a target for the early prevention of perinatal allergy sensitization.

  5. Immunoglobulin M

    DEFF Research Database (Denmark)

    Pleass, Richard J; Moore, Shona C; Stevenson, Liz

    2016-01-01

    Immunoglobulin M (IgM) is an ancient antibody class that is found in all vertebrates, with the exception of coelacanths, and is indispensable in both innate and adaptive immunity. The equally ancient human malaria parasite, Plasmodium falciparum, formed an intimate relationship with IgM with whic...

  6. Functional Versatility of AGY Serine Codons in Immunoglobulin Variable Region Genes

    Directory of Open Access Journals (Sweden)

    Thiago Detanico

    2016-11-01

    Full Text Available In systemic autoimmunity, autoantibodies directed against nuclear antigens (Ag often arise by somatic hypermutation (SHM that converts AGT and AGC (AGY Ser codons into Arg codons. This can occur by three different single-base changes. Curiously, AGY Ser codons are far more abundant in complementarity-determining regions (CDRs of IgV-region genes than expected for random codon use or from species-specific codon frequency data. CDR AGY codons are also more abundant than TCN Ser codons. We show that these trends hold even in cartilaginous fishes. Because AGC is a preferred target for SHM by activation-induced cytidine deaminase (AID, we asked whether the AGY abundance was solely due to a selection pressure to conserve high mutability in CDRs regardless of codon context but found that this was not the case. Instead, AGY triplets were selectively enriched in the Ser codon reading frame. Motivated by reports implicating a functional role for poly/autoreactive specificities in anti-viral antibodies, we also analyzed mutations at AGY in antibodies directed against a number of different viruses, and found that mutations producing Arg codons in anti-viral antibodies were indeed frequent. Unexpectedly, however, we also found that AGY codons mutated often to encode nearly all of the amino acids that are reported to provide the most frequent contacts with antigen (Ag. In many cases, mutations producing codons for these alternative amino acids in anti-viral antibodies were more frequent than those producing Arg codons. Mutations producing each of these key amino acids required only single-base changes in AGY. AGY is the only codon group in which 2/3rds of random mutations generate codons for these key residues. Finally, by directly analyzing x-ray structures of immune complexes from the RCSB protein database, we found that Ag-contact residues generated via somatic hypermutation occurred more often at AGY than at any other codon group. Thus, preservation of

  7. Detection of clonal B cells in microdissected reactive lymphoproliferations: possible diagnostic pitfalls in PCR analysis of immunoglobulin heavy chain gene rearrangement

    DEFF Research Database (Denmark)

    Zhou, X.G.; Sandvej, K.; Gregersen, Niels

    1999-01-01

    Aims-To evaluate the specificity of standard and fluorescence based (GENESCAN) polymerase chain reaction (PCR) immunoglobulin heavy chain (IgH) gene rearrangement analysis in complete and microdissected paraffin wax embedded sections from lymphoid proliferations. Methods-PCR IgH gene rearrangement...... because of preferential priming or detection of local B cell clones. Data from clonal analysis of small, microdissected or lymphocyte poor samples must be evaluated critically. It is recommended that analyses should be run in parallel on at least two tissue specimens. Only reproducible bands present...

  8. Catalytic immunoglobulin gene delivery in a mouse model of Alzheimer's disease: prophylactic and therapeutic applications.

    Science.gov (United States)

    Kou, Jinghong; Yang, Junling; Lim, Jeong-Eun; Pattanayak, Abhinandan; Song, Min; Planque, Stephanie; Paul, Sudhir; Fukuchi, Ken-Ichiro

    2015-02-01

    Accumulation of amyloid beta-peptide (Aβ) in the brain is hypothesized to be a causal event leading to dementia in Alzheimer's disease (AD). Aβ vaccination removes Aβ deposits from the brain. Aβ immunotherapy, however, may cause T cell- and/or Fc-receptor-mediated brain inflammation and relocate parenchymal Aβ deposits to blood vessels leading to cerebral hemorrhages. Because catalytic antibodies do not form stable immune complexes and Aβ fragments produced by catalytic antibodies are less likely to form aggregates, Aβ-specific catalytic antibodies may have safer therapeutic profiles than reversibly-binding anti-Aβ antibodies. Additionally, catalytic antibodies may remove Aβ more efficiently than binding antibodies because a single catalytic antibody can hydrolyze thousands of Aβ molecules. We previously isolated Aβ-specific catalytic antibody, IgVL5D3, with strong Aβ-hydrolyzing activity. Here, we evaluated the prophylactic and therapeutic efficacy of brain-targeted IgVL5D3 gene delivery via recombinant adeno-associated virus serotype 9 (rAAV9) in an AD mouse model. One single injection of rAAV9-IgVL5D3 into the right ventricle of AD model mice yielded widespread, high expression of IgVL5D3 in the unilateral hemisphere. IgVL5D3 expression was readily detectable in the contralateral hemisphere but to a much lesser extent. IgVL5D3 expression was also confirmed in the cerebrospinal fluid. Prophylactic and therapeutic injection of rAAV9-IgVL5D3 reduced Aβ load in the ipsilateral hippocampus of AD model mice. No evidence of hemorrhages, increased vascular amyloid deposits, increased proinflammatory cytokines, or infiltrating T-cells in the brains was found in the experimental animals. AAV9-mediated anti-Aβ catalytic antibody brain delivery can be prophylactic and therapeutic options for AD.

  9. Clinical significance of productive immunoglobulin heavy chain gene rearrangements in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Katsibardi, Katerina; Braoudaki, Maria; Papathanasiou, Chrissa; Karamolegou, Kalliopi; Tzortzatou-Stathopoulou, Fotini

    2011-09-01

    We analyzed the CDR3 region of 80 children with B-cell acute lymphoblastic leukemia (B-ALL) using the ImMunoGeneTics Information System and JOINSOLVER. In total, 108 IGH@ rearrangements were analyzed. Most of them (75.3%) were non-productive. IGHV@ segments proximal to IGHD-IGHJ@ were preferentially rearranged (45.3%). Increased utilization of IGHV3 segments IGHV3-13 (11.3%) and IGHV3-15 (9.3%), IGHD3 (30.5%), and IGHJ4 (34%) was noted. In pro-B ALL more frequent were IGHV3-11 (33.3%) and IGHV6-1 (33.3%), IGHD2-21 (50%), IGHJ4 (50%), and IGHJ6 (50%) segments. Shorter CDR3 length was observed in IGHV@6, IGHD7, and IGHJ1 segments, whereas increased CDR3 length was related to IGHV3, IGHD2, and IGHJ4 segments. Increased risk of relapse was found in patients with productive sequences. Specifically, the relapse-free survival rate at 5 years in patients with productive sequences at diagnosis was 75% (standard error [SE] ±9%), whereas in patients with non-productive sequences it was 97% (SE ±1.92%) (p-value =0.0264). Monoclonality and oligoclonality were identified in 81.2% and 18.75% cases at diagnosis, respectively. Sequence analysis revealed IGHV@ to IGHDJ joining only in 6.6% cases with oligoclonality. The majority (75%) of relapsed patients had monoclonal IGH@ rearrangements. The preferential utilization of IGHV@ segments proximal to IGHDJ depended on their location on the IGHV@ locus. Molecular mechanisms occurring during IGH@ rearrangement might play an essential role in childhood ALL prognosis. In our study, the productivity of the rearranged sequences at diagnosis proved to be a significant prognostic factor.

  10. Local Chromatin Features Including PU.1 and IKAROS Binding and H3K4 Methylation Shape the Repertoire of Immunoglobulin Kappa Genes Chosen for V(DJ Recombination

    Directory of Open Access Journals (Sweden)

    Louise S. Matheson

    2017-11-01

    Full Text Available V(DJ recombination is essential for the generation of diverse antigen receptor (AgR repertoires. In B cells, immunoglobulin kappa (Igκ light chain recombination follows immunoglobulin heavy chain (Igh recombination. We recently developed the DNA-based VDJ-seq assay for the unbiased quantitation of Igh VH and DH repertoires. Integration of VDJ-seq data with genome-wide datasets revealed that two chromatin states at the recombination signal sequence (RSS of VH genes are highly predictive of recombination in mouse pro-B cells. It is unknown whether local chromatin states contribute to Vκ gene choice during Igκ recombination. Here we adapt VDJ-seq to profile the Igκ VκJκ repertoire and present a comprehensive readout in mouse pre-B cells, revealing highly variable Vκ gene usage. Integration with genome-wide datasets for histone modifications, DNase hypersensitivity, transcription factor binding and germline transcription identified PU.1 binding at the RSS, which was unimportant for Igh, as highly predictive of whether a Vκ gene will recombine or not, suggesting that it plays a binary, all-or-nothing role, priming genes for recombination. Thereafter, the frequency with which these genes recombine was shaped both by the presence and level of enrichment of several other chromatin features, including H3K4 methylation and IKAROS binding. Moreover, in contrast to the Igh locus, the chromatin landscape of the promoter, as well as of the RSS, contributes to Vκ gene recombination. Thus, multiple facets of local chromatin features explain much of the variation in Vκ gene usage. Together, these findings reveal shared and divergent roles for epigenetic features and transcription factors in AgR V(DJ recombination and provide avenues for further investigation of chromatin signatures that may underpin V(DJ-mediated chromosomal translocations.

  11. Characterization of an Oct1 orthologue in the channel catfish, Ictalurus punctatus: A negative regulator of immunoglobulin gene transcription?

    NARCIS (Netherlands)

    Lennard, M.L.; Hikima, J.I.; Ross, D.A.; Kruiswijk, C.P.; Wilson, M.R.; Miller, N.W.; Warr, G.W.

    2007-01-01

    Background - The enhancer (E¿3') of the immunoglobulin heavy chain locus (IGH) of the channel catfish (Ictalurus punctatus) has been well characterized. The functional core region consists of two variant Oct transcription factor binding octamer motifs and one E-protein binding ¿E5 site. An

  12. Effects of an illicit cocktail on serum immunoglobulins, lymphocyte proliferation and cytokine gene expression in the veal calf

    International Nuclear Information System (INIS)

    Cantiello, Michela; Carletti, Monica; Cannizzo, Francesca T.; Nebbia, Carlo; Bellino, Claudio; Pie, Sandrine; Oswald, Isabelle P.; Bollo, Enrico; Dacasto, Mauro

    2007-01-01

    At the European Union level, the use of growth promoters (GPs) in cattle and other food-producing species is forbidden; nonetheless, the illicit use of anabolic hormones, β-agonists and corticosteroids, often administered in cocktails at lower concentrations to overcome control procedures, is still of public concern. The immune system (IS) is a multicomponent system that provide a coordinated response toward infectious diseases, not self-neoplasms and xenobiotics; in this respect, some GPs have been proved able to cause both morphological alterations in lymphoid organs and a modulating effect upon some immunological parameters. Therefore, in the present study the effects of an illicit cocktail upon the cattle IS functions were investigated by using some common endpoints adopted for the IS testing in humans. Twelve cross-bred male veal calves were divided in two experimental groups (n = 6); the first group was administered a cocktail of 17β-oestradiol (10 mg, 3 im injections at 17 days intervals), clenbuterol (20 μg kg -1 , per os for 40 days) and dexamethasone (4 mg per os for 6 days and, then, 5 mg for further 6 days) for a total of 55 days. The second one was used as control. Blood sampling were taken at T 0 and after 15 (T 1 ), 34 (T 2 ), 48 (T 3 ) days as well as the day before slaughtering (T 4 ). Immune endpoints considered were the thymus weight, the serum immunoglobulin G (IgG) and M (IgM) levels, the lymphocyte proliferation assay and the lymphocyte interleukins 1β and 8, tumour necrosis factor α and interferon γ (IFN-γ) gene expression levels. The administration of the illicit cocktail resulted in: (a) a reduction (P 1 , whereas in the second part of the study increasing levels (P 2 and T 4 for IgM and IgG, respectively) were recorded; (c) an overall reduction (P 1 ; in phytohaemagglutinin-stimulated cells, such a decrease was delayed up to T 2 (P 1 and T 2 . Taken together, present data suggest that GPs, even given in cocktails at sub

  13. A Comprehensive Analysis of the Phylogeny, Genomic Organization and Expression of Immunoglobulin Light Chain Genes in Alligator sinensis, an Endangered Reptile Species

    Science.gov (United States)

    Lu, Yan; Zhang, Chenglin; Wu, Xiaobing; Han, Haitang; Zhao, Yaofeng; Ren, Liming

    2016-01-01

    Crocodilians are evolutionarily distinct reptiles that are distantly related to lizards and are thought to be the closest relatives of birds. Compared with birds and mammals, few studies have investigated the Ig light chain of crocodilians. Here, employing an Alligator sinensis genomic bacterial artificial chromosome (BAC) library and available genome data, we characterized the genomic organization of the Alligator sinensis IgL gene loci. The Alligator sinensis has two IgL isotypes, λ and κ, the same as Anolis carolinensis. The Igλ locus contains 6 Cλ genes, each preceded by a Jλ gene, and 86 potentially functional Vλ genes upstream of (Jλ-Cλ)n. The Igκ locus contains a single Cκ gene, 6 Jκs and 62 functional Vκs. All VL genes are classified into a total of 31 families: 19 Vλ families and 12 Vκ families. Based on an analysis of the chromosomal location of the light chain genes among mammals, birds, lizards and frogs, the data further confirm that there are two IgL isotypes in the Alligator sinensis: Igλ and Igκ. By analyzing the cloned Igλ/κ cDNA, we identified a biased usage pattern of V families in the expressed Vλ and Vκ. An analysis of the junctions of the recombined VJ revealed the presence of N and P nucleotides in both expressed λ and κ sequences. Phylogenetic analysis of the V genes revealed V families shared by mammals, birds, reptiles and Xenopus, suggesting that these conserved V families are orthologous and have been retained during the evolution of IgL. Our data suggest that the Alligator sinensis IgL gene repertoire is highly diverse and complex and provide insight into immunoglobulin gene evolution in vertebrates. PMID:26901135

  14. A Comprehensive Analysis of the Phylogeny, Genomic Organization and Expression of Immunoglobulin Light Chain Genes in Alligator sinensis, an Endangered Reptile Species.

    Directory of Open Access Journals (Sweden)

    Xifeng Wang

    Full Text Available Crocodilians are evolutionarily distinct reptiles that are distantly related to lizards and are thought to be the closest relatives of birds. Compared with birds and mammals, few studies have investigated the Ig light chain of crocodilians. Here, employing an Alligator sinensis genomic bacterial artificial chromosome (BAC library and available genome data, we characterized the genomic organization of the Alligator sinensis IgL gene loci. The Alligator sinensis has two IgL isotypes, λ and κ, the same as Anolis carolinensis. The Igλ locus contains 6 Cλ genes, each preceded by a Jλ gene, and 86 potentially functional Vλ genes upstream of (Jλ-Cλn. The Igκ locus contains a single Cκ gene, 6 Jκs and 62 functional Vκs. All VL genes are classified into a total of 31 families: 19 Vλ families and 12 Vκ families. Based on an analysis of the chromosomal location of the light chain genes among mammals, birds, lizards and frogs, the data further confirm that there are two IgL isotypes in the Alligator sinensis: Igλ and Igκ. By analyzing the cloned Igλ/κ cDNA, we identified a biased usage pattern of V families in the expressed Vλ and Vκ. An analysis of the junctions of the recombined VJ revealed the presence of N and P nucleotides in both expressed λ and κ sequences. Phylogenetic analysis of the V genes revealed V families shared by mammals, birds, reptiles and Xenopus, suggesting that these conserved V families are orthologous and have been retained during the evolution of IgL. Our data suggest that the Alligator sinensis IgL gene repertoire is highly diverse and complex and provide insight into immunoglobulin gene evolution in vertebrates.

  15. Molecular analysis of immunoglobulin variable genes supports a germinal center experienced normal counterpart in primary cutaneous diffuse large B-cell lymphoma, leg-type.

    Science.gov (United States)

    Pham-Ledard, Anne; Prochazkova-Carlotti, Martina; Deveza, Mélanie; Laforet, Marie-Pierre; Beylot-Barry, Marie; Vergier, Béatrice; Parrens, Marie; Feuillard, Jean; Merlio, Jean-Philippe; Gachard, Nathalie

    2017-11-01

    Immunophenotype of primary cutaneous diffuse large B-cell lymphoma, leg-type (PCLBCL-LT) suggests a germinal center-experienced B lymphocyte (BCL2+ MUM1+ BCL6+/-). As maturation history of B-cell is "imprinted" during B-cell development on the immunoglobulin gene sequence, we studied the structure and sequence of the variable part of the genes (IGHV, IGLV, IGKV), immunoglobulin surface expression and features of class switching in order to determine the PCLBCL-LT cell of origin. Clonality analysis with BIOMED2 protocol and VH leader primers was done on DNA extracted from frozen skin biopsies on retrospective samples from 14 patients. The clonal DNA IGHV sequence of the tumor was aligned and compared with the closest germline sequence and homology percentage was calculated. Superantigen binding sites were studied. Features of selection pressure were evaluated with the multinomial Lossos model. A functional monoclonal sequence was observed in 14 cases as determined for IGHV (10), IGLV (2) or IGKV (3). IGV mutation rates were high (>5%) in all cases but one (median:15.5%), with superantigen binding sites conservation. Features of selection pressure were identified in 11/12 interpretable cases, more frequently negative (75%) than positive (25%). Intraclonal variation was detected in 3 of 8 tumor specimens with a low rate of mutations. Surface immunoglobulin was an IgM in 12/12 cases. FISH analysis of IGHM locus, deleted during class switching, showed heterozygous IGHM gene deletion in half of cases. The genomic PCR analysis confirmed the deletions within the switch μ region. IGV sequences were highly mutated but functional, with negative features of selection pressure suggesting one or more germinal center passage(s) with somatic hypermutation, but superantigen (SpA) binding sites conservation. Genetic features of class switch were observed, but on the non functional allele and co-existing with primary isotype IgM expression. These data suggest that cell-of origin is

  16. HCV Proteins and Immunoglobulin Variable Gene (IgV Subfamilies in HCV-Induced Type II Mixed Cryoglobulinemia: A Concurrent Pathogenetic Role

    Directory of Open Access Journals (Sweden)

    Giuseppe Sautto

    2012-01-01

    Full Text Available The association between hepatitis C virus (HCV infection and type II mixed cryoglobulinemia (MCII is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV gene subfamilies frequently endowed with rheumatoid factor (RF activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved.

  17. HCV proteins and immunoglobulin variable gene (IgV) subfamilies in HCV-induced type II mixed cryoglobulinemia: a concurrent pathogenetic role.

    Science.gov (United States)

    Sautto, Giuseppe; Mancini, Nicasio; Solforosi, Laura; Diotti, Roberta A; Clementi, Massimo; Burioni, Roberto

    2012-01-01

    The association between hepatitis C virus (HCV) infection and type II mixed cryoglobulinemia (MCII) is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV) gene subfamilies frequently endowed with rheumatoid factor (RF) activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved.

  18. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936

    NARCIS (Netherlands)

    van Dongen, J. J. M.; Langerak, A. W.; Brüggemann, M.; Evans, P. A. S.; Hummel, M.; Lavender, F. L.; Delabesse, E.; Davi, F.; Schuuring, E.; García-Sanz, R.; van Krieken, J. H. J. M.; Droese, J.; González, D.; Bastard, C.; White, H. E.; Spaargaren, M.; González, M.; Parreira, A.; Smith, J. L.; Morgan, G. J.; Kneba, M.; Macintyre, E. A.

    2003-01-01

    In a European BIOMED-2 collaborative study, multiplex PCR assays have successfully been developed and standardized for the detection of clonally rearranged immunoglobulin (Ig) and T-cell receptor (TCR) genes and the chromosome aberrations t(11; 14) and t(14; 18). This has resulted in 107 different

  19. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936.

    NARCIS (Netherlands)

    Dongen, J.J.M. van; Langerak, A.W.; Bruggemann, M.; Evans, P.; Hummel, M.; Lavender, F.L.; Delabesse, E.; Davi, F.; Schuuring, E.; Garcia-Sanz, R.; Krieken, J.H.J.M. van; Droese, J.; Gonzalez, D.; Bastard, C.; White, H.E.; Spaargaren, M.C.; Gonzalez, M.; Parreira, A.; Smith, J.L.; Morgan, G.J.; Kneba, M.; Macintyre, E.A.

    2003-01-01

    In a European BIOMED-2 collaborative study, multiplex PCR assays have successfully been developed and standardized for the detection of clonally rearranged immunoglobulin (Ig) and T-cell receptor (TCR) genes and the chromosome aberrations t(11;14) and t(14;18). This has resulted in 107 different

  20. Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936.

    NARCIS (Netherlands)

    Evans, P.A.; Pott, C.; Groenen, P.J.T.A.; Salles, G.; Davi, F.; Berger, F.; Garcia, J.F.; Krieken, J.H.J.M. van; Pals, S.; Kluin, P.; Schuuring, E.; Spaargaren, M.; Boone, E.; Gonzalez, D.; Martinez, B.; Villuendas, R.; Gameiro, P.; Diss, T.C.; Mills, K.; Morgan, G.J.; Carter, G.I.; Milner, B.J.; Pearson, D.; Hummel, M.; Jung, W.; Ott, M.; Canioni, D.; Beldjord, K.; Bastard, C.; Delfau-Larue, M.H.; Dongen, J.J.M. van; Molina, T.J.; Cabecadas, J.

    2007-01-01

    Polymerase chain reaction (PCR) assessment of clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements is an important diagnostic tool in mature B-cell neoplasms. However, lack of standardized PCR protocols resulting in a high level of false negativity has hampered comparability of

  1. Local Chromatin Features Including PU.1 and IKAROS Binding and H3K4 Methylation Shape the Repertoire of Immunoglobulin Kappa Genes Chosen for V(D)J Recombination

    OpenAIRE

    Louise S. Matheson; Daniel J. Bolland; Peter Chovanec; Felix Krueger; Simon Andrews; Hashem Koohy; Anne E. Corcoran

    2017-01-01

    V(D)J recombination is essential for the generation of diverse antigen receptor (AgR) repertoires. In B cells, immunoglobulin kappa (Igκ) light chain recombination follows immunoglobulin heavy chain (Igh) recombination. We recently developed the DNA-based VDJ-seq assay for the unbiased quantitation of Igh VH and DH repertoires. Integration of VDJ-seq data with genome-wide datasets revealed that two chromatin states at the recombination signal sequence (RSS) of VH genes are highly predictive o...

  2. Primary cutaneous B-cell lymphoma is associated with somatically hypermutated immunoglobulin variable genes and frequent use of VH1-69 and VH4-59 segments.

    Science.gov (United States)

    Perez, M; Pacchiarotti, A; Frontani, M; Pescarmona, E; Caprini, E; Lombardo, G A; Russo, G; Faraggiana, T

    2010-03-01

    Accurate assessment of the somatic mutational status of clonal immunoglobulin variable region (IgV) genes is relevant in elucidating tumour cell origin in B-cell lymphoma; virgin B cells bear unmutated IgV genes, while germinal centre and postfollicular B cells carry mutated IgV genes. Furthermore, biases in the IgV repertoire and distribution pattern of somatic mutations indicate a possible antigen role in the pathogenesis of B-cell malignancies. This work investigates the cellular origin and antigenic selection in primary cutaneous B-cell lymphoma (PCBCL). We analysed the nucleotide sequence of clonal IgV heavy-chain gene (IgVH) rearrangements in 51 cases of PCBCL (25 follicle centre, 19 marginal zone and seven diffuse large B-cell lymphoma, leg-type) and compared IgVH sequences with their closest germline segment in the GenBank database. Molecular data were then correlated with histopathological features. We showed that all but one of the 51 IgVH sequences analysed exhibited extensive somatic hypermutations. The detected mutation rate ranged from 1.6% to 21%, with a median rate of 9.8% and was independent of PCBCL histotype. Calculation of antigen-selection pressure showed that 39% of the mutated IgVH genes displayed a number of replacement mutations and silent mutations in a pattern consistent with antigenic selection. Furthermore, two segments, VH1-69 (12%) and VH4-59 (14%), were preferentially used in our case series. Data indicate that neoplastic B cells of PBCBL have experienced germinal centre reaction and also suggest that the involvement of IgVH genes is not entirely random in PCBCL and that common antigen epitopes could be pathologically relevant in cutaneous lymphomagenesis.

  3. Mutation Status and Immunoglobulin Gene Rearrangements in Patients from Northwest and Central Region of Spain with Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    I. González-Gascón y Marín

    2014-01-01

    Full Text Available The aim of this study was to investigate the frequency and mutation status of the immunoglobulin heavy variable chain (IGHV in a cohort of 224 patients from northwest and central region of Spain diagnosed with chronic lymphocytic leukemia (CLL, and to correlate it with cytogenetic abnormalities, overall survival (OS and time to first treatment (TTFT. 125 patients had mutated IGHV, while 99 had unmutated IGHV. The most frequently used IGHV family was IGHV3, followed by IGHV1 and IGHV4. The regions IGHV3-30, IGHV1-69, IGHV3-23, and IGHV4-34 were the most commonly used. Only 3.1% of the patients belonged to the subfamily IGHV3-21 and we failed to demonstrate a worse clinical outcome in this subgroup. The IGHV4 family appeared more frequently with mutated pattern, similar to IGHV3-23 and IGHV3-74. By contrast, IGHV1-69 was expressed at a higher frequency in unmutated CLL patients. All the cases from IGHV3-11 and almost all from IGHV5-51 subfamily belonged to the group of unmutated CLL.

  4. Asian population frequencies and haplotype distribution of killer cell immunoglobulin-like receptor (KIR) genes among Chinese, Malay, and Indian in Singapore.

    Science.gov (United States)

    Lee, Yi Chuan; Chan, Soh Ha; Ren, Ee Chee

    2008-11-01

    Killer cell immunoglobulin-like receptors (KIR) gene frequencies have been shown to be distinctly different between populations and contribute to functional variation in the immune response. We have investigated KIR gene frequencies in 370 individuals representing three Asian populations in Singapore and report here the distribution of 14 KIR genes (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) with two pseudogenes (2DP1, 3DP1) among Singapore Chinese (n = 210); Singapore Malay (n = 80), and Singapore Indian (n = 80). Four framework genes (KIR3DL3, 3DP1, 2DL4, 3DL2) and a nonframework pseudogene 2DP1 were detected in all samples while KIR2DS2, 2DL2, 2DL5, and 2DS5 had the greatest significant variation across the three populations. Fifteen significant linkage patterns, consistent with associations between genes of A and B haplotypes, were observed. Eighty-four distinct KIR profiles were determined in our populations, 38 of which had not been described in other populations. KIR haplotype studies were performed using nine Singapore Chinese families comprising 34 individuals. All genotypes could be resolved into corresponding pairs of existing haplotypes with eight distinct KIR genotypes and eight different haplotypes. The haplotype A2 with frequency of 63.9% was dominant in Singapore Chinese, comparable to that reported in Korean and Chinese Han. The A haplotypes predominate in Singapore Chinese, with ratio of A to B haplotypes of approximately 3:1. Comparison with KIR frequencies in other populations showed that Singapore Chinese shared similar distributions with Chinese Han, Japanese, and Korean; Singapore Indian was found to be comparable with North Indian Hindus while Singapore Malay resembled the Thai.

  5. Physical linkage of a human immunoglobulin heavy chain variable region gene segment to diversity and joining region elements

    International Nuclear Information System (INIS)

    Schroeder, H.W. Jr.; Walter, M.A.; Hofker, M.H.; Ebens, A.; Van Dijk, K.W.; Liao, L.C.; Cox, D.W.; Milner, E.C.B.; Perlmutter, R.M.

    1988-01-01

    Antibody genes are assembled from a series of germ-line gene segments that are juxtaposed during the maturation of B lymphocytes. Although diversification of the adult antibody repertoire results in large part from the combinatorial joining of these gene segments, a restricted set of antibody heavy chain variable (V H ), diversity (D H ), and joining (J H ) region gene segments appears preferentially in the human fetal repertoire. The authors report here that one of these early-expressed V H elements (termed V H 6) is the most 3' V H gene segment, positioned 77 kilobases on the 5' side of the J H locus and immediately adjacent to a set of previously described D H sequences. In addition to providing a physical map linking human V H , D H , and J H elements, these results support the view that the programmed development of the antibody V H repertoire is determined in part by the chromosomal position of these gene segments

  6. Clonal progression during the T cell-dependent B cell antibody response depends on the immunoglobulin DH gene segment repertoire.

    Directory of Open Access Journals (Sweden)

    Ahmad eTrad

    2014-08-01

    Full Text Available The diversity of the third complementarity determining region of the Ig H chain is constrained by natural selection of immunoglobulin diversity (DH sequence. To test the functional significance of this constraint in the context of thymus-dependent (TD immune responses, we immunized BALB/c mice with WT or altered DH sequence with 2-phenyloxazolone-coupled chicken serum albumin (phOx-CSA. We chose this antigen because studies of the humoral immune response to the hapten phOx were instrumental in the development of the current theoretical framework on which our understanding of the forces driving TD responses is based. To allow direct comparison, we used the classic approach of generating monoclonal Ab (mAb from various stages of the immune response to phOx to assess the effect of changing the sequence of the DH on clonal expansion, class switching and affinity maturation, which are hallmarks of TD responses. Compared to WT, TD-induced humoral IgM as well as IgG antibody production in the D-altered D-DFS and D-iD strains were significantly reduced. An increased prevalence of IgM producing hybridomas from late primary, secondary, and tertiary memory responses suggested either impaired class switch recombination (CSR or impaired clonal expansion of class switched B cells with phOx reactivity. Neither of the D-altered strains demonstrated the restriction in the VH/VL repertoire, the elimination of VH1 family-encoded antibodies, the focusing of the distribution of CDR-H3 lengths, or the selection for the normally dominant Ox1 clonotype which all are hallmarks of the anti-phOx response in WT mice. These changes in clonal selection and expansion as well as class switch recombination indicate that the genetic constitution of the DH locus, which has been selected by evolution, can strongly influence the functional outcome of a TD humoral response.

  7. Immunoglobulins in Cerebrospinal Fluid

    DEFF Research Database (Denmark)

    Sellebjerg, Finn Thorup

    2015-01-01

    immunoglobulin synthesis. Intrathecally synthesised immunoglobulins are usually of restricted clonality, and electrophoresis-based methods can be used for detecting this in the form of oligoclonal bands. These methods depend on comparing paired CSF and blood samples. Qualitative analyses for the assessment......The assessment of intrathecally synthesised immunoglobulin is an important part of routine cerebrospinal fl uid (CSF) analysis. Immunoglobulins can be detected in normal CSF and are derived from plasma. The appearance of immunoglobulins in normal CSF is readily explained by size-dependent diffusion...

  8. Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles.

    Science.gov (United States)

    Gadala-Maria, Daniel; Yaari, Gur; Uduman, Mohamed; Kleinstein, Steven H

    2015-02-24

    Individual variation in germline and expressed B-cell immunoglobulin (Ig) repertoires has been associated with aging, disease susceptibility, and differential response to infection and vaccination. Repertoire properties can now be studied at large-scale through next-generation sequencing of rearranged Ig genes. Accurate analysis of these repertoire-sequencing (Rep-Seq) data requires identifying the germline variable (V), diversity (D), and joining (J) gene segments used by each Ig sequence. Current V(D)J assignment methods work by aligning sequences to a database of known germline V(D)J segment alleles. However, existing databases are likely to be incomplete and novel polymorphisms are hard to differentiate from the frequent occurrence of somatic hypermutations in Ig sequences. Here we develop a Tool for Ig Genotype Elucidation via Rep-Seq (TIgGER). TIgGER analyzes mutation patterns in Rep-Seq data to identify novel V segment alleles, and also constructs a personalized germline database containing the specific set of alleles carried by a subject. This information is then used to improve the initial V segment assignments from existing tools, like IMGT/HighV-QUEST. The application of TIgGER to Rep-Seq data from seven subjects identified 11 novel V segment alleles, including at least one in every subject examined. These novel alleles constituted 13% of the total number of unique alleles in these subjects, and impacted 3% of V(D)J segment assignments. These results reinforce the highly polymorphic nature of human Ig V genes, and suggest that many novel alleles remain to be discovered. The integration of TIgGER into Rep-Seq processing pipelines will increase the accuracy of V segment assignments, thus improving B-cell repertoire analyses.

  9. Direct interactions of OCA-B and TFII-I regulate immunoglobulin heavy-chain gene transcription by facilitating enhancer-promoter communication.

    Science.gov (United States)

    Ren, Xiaodi; Siegel, Rachael; Kim, Unkyu; Roeder, Robert G

    2011-05-06

    B cell-specific coactivator OCA-B, together with Oct-1/2, binds to octamer sites in promoters and enhancers to activate transcription of immunoglobulin (Ig) genes, although the mechanisms underlying their roles in enhancer-promoter communication are unknown. Here, we demonstrate a direct interaction of OCA-B with transcription factor TFII-I, which binds to DICE elements in Igh promoters, that affects transcription at two levels. First, OCA-B relieves HDAC3-mediated Igh promoter repression by competing with HDAC3 for binding to promoter-bound TFII-I. Second, and most importantly, Igh 3' enhancer-bound OCA-B and promoter-bound TFII-I mediate promoter-enhancer interactions, in both cis and trans, that are important for Igh transcription. These and other results reveal an important function for OCA-B in Igh 3' enhancer function in vivo and strongly favor an enhancer mechanism involving looping and facilitated factor recruitment rather than a tracking mechanism. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Analysis of S gene mutation of the hepatitis B virus in adult liver transplant recipients showing resistance to hepatitis B immunoglobulin therapy.

    Science.gov (United States)

    Park, G-C; Hwang, S; Ahn, C-S; Kim, K-H; Moon, D-B; Ha, T-Y; Song, G-W; Jung, D-H; Shin, Y W; Kim, S-H; Chang, K-H; Namgoong, J-M; Park, C-S; Park, H-W; Park, Y-H; Kang, S-H; Jung, B-H; Lee, S-G

    2013-10-01

    A considerable proportion of recipients of liver transplantations who are presented hepatitis B immunoglobulin (HBIG) monotherapy for hepatitis B virus (HBV) prophylaxis develop HBIG resistance. In this study, we investigated the mutation patterns in the major hydrophilic region (MHR) of amino acid sequences 100 to 160. Using the gene sequence analyzer for amino acid sequences 0 to 226 in the S/pre-S region we analyzed blood samples of 15 patients showing HBIG resistance after high-dose HBIG prophylaxis. Various mutations in the MHR were observed in 14/15 samples: Gly145Arg mutation in 8/13 Adr subtype and 1/2 Ayw subtype samples (60%). The next most common mutation was Gly165Trp in 8/13 Adr subtype but neither of 2 Ayw subtype samples (53.3%). Concurrent antiviral resistance was noted in 5 patients: lamivudine (n = 5), or entecavir (n = 3), but not adefovir, suggesting the occurrence of simultaneous, antiviral cross-resistances. Two patients underwent retransplantation due to the progression of HBV infection despite vigorous antiviral therapy. At diagnosis of HBV recurrence, the mean HBV DNA load was 6.5 × 10(6) copies/mL; 4 patients showed paradoxical coexistence of anti-HBs and HBsAg. Currently, 2 subjects show low-level HBV DNA replication in peripheral blood, although the other 12 had no DNA replication after prolonged antiviral therapy. This study suggested that various mutations in the "a" determinant were associated with HBIG resistance. Since treatment failure to rescue antiviral therapy was often associated with delayed detection of HBV recurrence rather than concurrent antiviral resistance, frequent HBV surveillance using more sensitive screening tests, such as HBeAg and HBV DNA polymerase chain reaction assay, seems to be mandatory. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Local Chromatin Features Including PU.1 and IKAROS Binding and H3K4 Methylation Shape the Repertoire of Immunoglobulin Kappa Genes Chosen for V(D)J Recombination.

    Science.gov (United States)

    Matheson, Louise S; Bolland, Daniel J; Chovanec, Peter; Krueger, Felix; Andrews, Simon; Koohy, Hashem; Corcoran, Anne E

    2017-01-01

    V(D)J recombination is essential for the generation of diverse antigen receptor (AgR) repertoires. In B cells, immunoglobulin kappa ( Igκ ) light chain recombination follows immunoglobulin heavy chain ( Igh ) recombination. We recently developed the DNA-based VDJ-seq assay for the unbiased quantitation of Igh VH and DH repertoires. Integration of VDJ-seq data with genome-wide datasets revealed that two chromatin states at the recombination signal sequence (RSS) of VH genes are highly predictive of recombination in mouse pro-B cells. It is unknown whether local chromatin states contribute to Vκ gene choice during Igκ recombination. Here we adapt VDJ-seq to profile the Igκ VκJκ repertoire and present a comprehensive readout in mouse pre-B cells, revealing highly variable Vκ gene usage. Integration with genome-wide datasets for histone modifications, DNase hypersensitivity, transcription factor binding and germline transcription identified PU.1 binding at the RSS, which was unimportant for Igh , as highly predictive of whether a Vκ gene will recombine or not, suggesting that it plays a binary, all-or-nothing role, priming genes for recombination. Thereafter, the frequency with which these genes recombine was shaped both by the presence and level of enrichment of several other chromatin features, including H3K4 methylation and IKAROS binding. Moreover, in contrast to the Igh locus, the chromatin landscape of the promoter, as well as of the RSS, contributes to Vκ gene recombination. Thus, multiple facets of local chromatin features explain much of the variation in Vκ gene usage. Together, these findings reveal shared and divergent roles for epigenetic features and transcription factors in AgR V(D)J recombination and provide avenues for further investigation of chromatin signatures that may underpin V(D)J-mediated chromosomal translocations.

  12. Immunoglobulins for preventing hepatitis A

    DEFF Research Database (Denmark)

    Liu, Jian Ping; Nikolova, Dimitrinka; Fei, Yutong

    2009-01-01

    Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention.......Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention....

  13. Immunoglobulin and fatty acids

    DEFF Research Database (Denmark)

    2009-01-01

    The present invention relates to a composition comprising 0.1-10 w/w % immunoglobulin (Ig), 4-14 w/w % saturated fatty acids, 4-14 w/w % mono-unsaturated fatty acids and 0-5 w/w % poly-unsaturated fatty acids, wherein the weight percentages are based on the content of dry matter in the composition...

  14. [Production, specificity and structure of immunoglobulins].

    Science.gov (United States)

    Goujard, C; Delfraissy, J F

    1991-03-21

    Immunoglobulin is a key factor of the immune response resulting from B-cell activation and associated with T-cell stimulation. Because of its structure, this antibody has a dual function: it specifically recognizes the inducer antigen in the variable region and eliminates it by a constant portion which is responsible for effector properties. Surface immunoglobulin, therefore, is the B-cell antigen receptor; it differs from the T-cell receptor in that it recognizes the antigen unbound to the major istocompatibility complex; binding the antigen results in direct signal transduction first in the cytoplasm, then in the nucleus. This receptor can be secreted in the body: it is made up of circulating immunoglobulins. Human immunoglobulins are divided into 5 classes, each of them with its own response kinetics, distribution and functions. The variability of the antibody response accounts for a genetic organization involving numerous genes which may be associated with each other, or mutate, or recombine during maturation of the lymphocytes. Altogether, this system has a theoretical capacity of response to three hundred million different antigens.

  15. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936 : Report of the BIOMED-2 Concerted Action BMH4-CT98-3936

    NARCIS (Netherlands)

    van Dongen, J.J.M.; Langerak, A.W.; Bruggemann, M.; Evans, P.A.S.; Hummel, M.; Lavender, F.L.; Delabesse, E.; Davi, F.; Schuuring, E.; Garcia-Sanz, R.; Van Krieken, J.H.J.M.; Droese, J.; Gonzalez, D.; Bastard, C.; White, H.E.; Spaargaren, M.; Gonzalez, M.; Parreira, A.; Smith, J.L.; Morgan, G.J.; Kneba, M.; Macintyre, E.A.

    2003-01-01

    In a European BIOMED-2 collaborative study, multiplex PCR assays have successfully been developed and standardized for the detection of clonally rearranged immunoglobulin (Ig) and T-cell receptor (TCR) genes and the chromosome aberrations t(11; 14) and t(14; 18). This has resulted in 107 different

  16. The interaction between calreticulin and immunoglobulin G and immunoglobulin Y

    DEFF Research Database (Denmark)

    Møllegaard, Karen Mai; Duus, Karen; Træholt, Sofie Dietz

    2011-01-01

    accumulating in support of calreticulin as a polypeptide binding chaperone. In contrast to mammalian immunoglobulin G (IgG), which has complex type N-glycans, chicken immunoglobulin Y (IgY) possesses a monoglucosylated high mannose N-linked glycan, which is a ligand for calreticulin. Here, we have used solid...... and solution-phase assays to analyze the in vitro binding of calreticulin, purified from human placenta, to human IgG and chicken IgY in order to compare the interactions. In addition, peptides from the respective immunoglobulins were included to further probe the binding specificity of calreticulin....... The experiments demonstrate the ability of calreticulin to bind to denatured forms of both IgG and IgY regardless of the glycosylation state of the proteins. Furthermore, calreticulin exhibits binding to peptides (glycosylated and non-glycosylated) derived from trypsin digestion of both immunoglobulins...

  17. MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils

    Science.gov (United States)

    Campo, Vanina A.; Patenaude, Anne-Marie; Kaden, Svenja; Horb, Lori; Firka, Daniel; Jiricny, Josef; Di Noia, Javier M.

    2013-01-01

    The mammalian antibody repertoire is shaped by somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin (Ig) loci of B lymphocytes. SHM and CSR are triggered by non-canonical, error-prone processing of G/U mismatches generated by activation-induced deaminase (AID). In birds, AID does not trigger SHM, but it triggers Ig gene conversion (GC), a ‘homeologous’ recombination process involving the Ig variable region and proximal pseudogenes. Because recombination fidelity is controlled by the mismatch repair (MMR) system, we investigated whether MMR affects GC in the chicken B cell line DT40. We show here that Msh6−/− and Pms2−/− DT40 cells display cell cycle defects, including genomic re-replication. However, although IgVλ GC tracts in MMR-deficient cells were slightly longer than in normal cells, Ig GC frequency, donor choice or the number of mutations per sequence remained unaltered. The finding that the avian MMR system, unlike that of mammals, does not seem to contribute towards the processing of G/U mismatches in vitro could explain why MMR is unable to initiate Ig GC in this species, despite initiating SHM and CSR in mammalian cells. Moreover, as MMR does not counteract or govern Ig GC, we report a rare example of ‘homeologous’ recombination insensitive to MMR. PMID:23314153

  18. Three monoclonal antibodies to the VHS virus glycoprotein: comparison of reactivity in relation to differences in immunoglobulin variable domain gene sequences

    DEFF Research Database (Denmark)

    Lorenzen, Niels; Cupit, P.M.; Secombes, C.J.

    2000-01-01

    and their neutralising activity was evident. Binding kinetic analyses by plasmon resonance identified differences in the dissociation rate constant (kd) as a possible explanation for the different reactivity levels of the MAbs. The Ig variable heavy (VH) and light (V kappa) domain gene sequences of the three hybridomas...... were compared. The inferred amino acid sequence of the two neutralising antibody VH domains differed by three amino acid residues (97% identity) and only one residue difference was evident in the Vk. domains. In contrast, IP1H3 shared only 38 and 39% identity with the 3F1A2 and 3F1H10 VH domains...... respectively and 49 and 50% identity with the 3F1A2 and 3F1H10 VK domains respectively. The neutralising antibodies were produced by hybridomas originating from the same fusion and the high nucleotide sequence homology of the variable Ig gene regions indicated that the plasma cell partners of the hybridomas...

  19. Immunoglobulin Heavy Chain Variable Region and Major Histocompatibility Region Genes Are Linked to Induced Graves' Disease in Females From Two Very Large Families of Recombinant Inbred Mice

    Science.gov (United States)

    Aliesky, Holly; Banuelos, Bianca; Magana, Jessica; Williams, Robert W.; Rapoport, Basil

    2014-01-01

    Graves' hyperthyroidism is caused by antibodies to the TSH receptor (TSHR) that mimic thyroid stimulation by TSH. Stimulating TSHR antibodies and hyperthyroidism can be induced by immunizing mice with adenovirus expressing the human TSHR A-subunit. Prior analysis of induced Graves' disease in small families of recombinant inbred (RI) female mice demonstrated strong genetic control but did not resolve trait loci for TSHR antibodies or elevated serum T4. We investigated the genetic basis for induced Graves' disease in female mice of two large RI families and combined data with earlier findings to provide phenotypes for 178 genotypes. TSHR antibodies measured by inhibition of TSH binding to its receptor were highly significantly linked in the BXD set to the major histocompatibility region (chromosome 17), consistent with observations in 3 other RI families. In the LXS family, we detected linkage between T4 levels after TSHR-adenovirus immunization and the Ig heavy chain variable region (Igvh, chromosome 12). This observation is a key finding because components of the antigen binding region of Igs determine antibody specificity and have been previously linked to induced thyroid-stimulating antibodies. Data from the LXS family provide the first evidence in mice of a direct link between induced hyperthyroidism and Igvh genes. A role for major histocompatibility genes has now been established for genetic susceptibility to Graves' disease in both humans and mice. Future studies using arrays incorporating variation in the complex human Ig gene locus will be necessary to determine whether Igvh genes are also linked to Graves' disease in humans. PMID:25051451

  20. Indirect Enzyme-Linked Immunosorbent Assay for Detection of Immunoglobulin G Reactive with a Recombinant Protein Expressed from the Gene Encoding the 116-Kilodalton Protein of Mycoplasma pneumoniae

    OpenAIRE

    Duffy, Michael F.; Whithear, Kevin G.; Noormohammadi, Amir H.; Markham, Philip F.; Catton, Michael; Leydon, Jennie; Browning, Glenn F.

    1999-01-01

    Serology remains the method of choice for laboratory diagnosis of Mycoplasma pneumoniae infection. Currently available serological tests employ complex cellular fractions of M. pneumoniae as antigen. To improve the specificity of M. pneumoniae diagnosis, a recombinant protein was assessed as a serodiagnostic reagent. A panel of recombinant proteins were expressed from a cloned M. pneumoniae gene that encodes a 116-kDa surface protein antigen. The recombinant proteins were assessed for reactiv...

  1. Clinical applications of immunoglobulin: update

    Directory of Open Access Journals (Sweden)

    Marcia Cristina Zago Novaretti

    2011-06-01

    Full Text Available Human immunoglobulin is the most used blood product in the clinical practice. Immunoglobulin applications have increased quickly since the elucidation of its immunomodulatory and antiinflammatory properties which turned this blood product into a precious tool in the treatment of numerous diseases that present with humoral immune deficiency or that cause immune system dysfunction. Currently, the approved indications for Ig are: primary immunodeficiencies, secondary immunodeficiencies (multiple myeloma or chronic lymphoid leukemia, Kawasaki syndrome, immune thrombocytopenic purpura, Guillain Barré syndrome, graft-versus-host disease following bone marrow transplantation and repeat infections in HIV children. On the other hand, there are numerous "off-label" indications of immunoglobulin, which represent 20-60% of all clinical applications of this drug. It is important to study all these indications and, above all, the scientific evidence for its use, in order to provide patients with a new therapeutic option without burdening the health system. This review results from a wide selection of papers identified in the Pubmed and Lilacs scientific electronic databases. A group of descriptors were used from human immunoglobulin to the names of each disease that immunoglobulin is clinically applied. Our main objective is to list the numerous indications of immunoglobulin, both authorized and "off-label" and to analyze these indications in the light of the most recent scientific evidence.

  2. HIV exposed seronegative (HESN compared to HIV infected individuals have higher frequencies of telomeric Killer Immunoglobulin-like Receptor (KIR B motifs; Contribution of KIR B motif encoded genes to NK cell responsiveness.

    Directory of Open Access Journals (Sweden)

    Elise Jackson

    Full Text Available Previously, we showed that Killer Immunoglobulin-like Receptor (KIR3DS1 homozygotes (hmz are more frequent in HIV exposed seronegative (HESN than in recently HIV infected (HIV+ individuals. KIR3DS1 encodes an activating Natural Killer (NK cell receptor (NKR. The link between KIR genotype and HIV outcomes likely arises from the function that NK cells acquire through expression of particular NKRs. An initial screen of 97 HESN and 123 HIV+ subjects for the frequency of KIR region gene carriage observed between-group differences for several telomeric KIR region loci. In a larger set of up to 106 HESN and 439 HIV+ individuals, more HESN than HIV+ subjects were KIR3DS1 homozygotes, lacked a full length KIR2DS4 gene and carried the telomeric group B KIR haplotype motif, TB01. TB01 is characterized by the presence of KIR3DS1, KIR2DL5A, KIR2DS3/5 and KIR2DS1, in linkage disequilibrium with each other. We assessed which of the TB01 encoded KIR gene products contributed to NK cell responsiveness by stimulating NK cells from 8 HIV seronegative KIR3DS1 and TB01 motif homozygotes with 721.221 HLA null cells and evaluating the frequency of KIR3DS1+/-KIR2DL5+/-, KIR3DS1+/-KIR2DS1+/-, KIR3DS1+/-KIR2DS5+/- NK cells secreting IFN-γ and/or expressing CD107a. A higher frequency of NK cells expressing, versus not, KIR3DS1 responded to 721.221 stimulation. KIR2DL5A+, KIR2DS1+ and KIR2DS5+ NK cells did not contribute to 721.221 responses or modulate those by KIR3DS1+ NK cells. Thus, of the TB01 KIR gene products, only KIR3DS1 conferred responsiveness to HLA-null stimulation, demonstrating its ligation can activate ex vivo NK cells.

  3. Violation of an evolutionarily conserved immunoglobulin diversity gene sequence preference promotes production of dsDNA-specific IgG antibodies.

    Directory of Open Access Journals (Sweden)

    Aaron Silva-Sanchez

    Full Text Available Variability in the developing antibody repertoire is focused on the third complementarity determining region of the H chain (CDR-H3, which lies at the center of the antigen binding site where it often plays a decisive role in antigen binding. The power of VDJ recombination and N nucleotide addition has led to the common conception that the sequence of CDR-H3 is unrestricted in its variability and random in its composition. Under this view, the immune response is solely controlled by somatic positive and negative clonal selection mechanisms that act on individual B cells to promote production of protective antibodies and prevent the production of self-reactive antibodies. This concept of a repertoire of random antigen binding sites is inconsistent with the observation that diversity (DH gene segment sequence content by reading frame (RF is evolutionarily conserved, creating biases in the prevalence and distribution of individual amino acids in CDR-H3. For example, arginine, which is often found in the CDR-H3 of dsDNA binding autoantibodies, is under-represented in the commonly used DH RFs rearranged by deletion, but is a frequent component of rarely used inverted RF1 (iRF1, which is rearranged by inversion. To determine the effect of altering this germline bias in DH gene segment sequence on autoantibody production, we generated mice that by genetic manipulation are forced to utilize an iRF1 sequence encoding two arginines. Over a one year period we collected serial serum samples from these unimmunized, specific pathogen-free mice and found that more than one-fifth of them contained elevated levels of dsDNA-binding IgG, but not IgM; whereas mice with a wild type DH sequence did not. Thus, germline bias against the use of arginine enriched DH sequence helps to reduce the likelihood of producing self-reactive antibodies.

  4. Comparative mapping of DNA probes derived from the V{sub k} immunoglobulin gene regions on human and great ape chromosomes by fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, N.; Wienberg, J.; Ermert, K. [Universitaet Muenchen (Germany)] [and others

    1995-03-01

    Fluorescence in situ hybridization (FISH) of cosmid clones of human V{sub K} gene regions to human and primate chromosomes contributed to the dating of chromosome reorganizations in evolution. A clone from the K locus at 2p11-p12 (cos 106) hybridized to the assumed homologous chromosome bands in the chimpanzees Pan troglodytes (PTR) and P. paniscus (PPA), the Gorilla gorilla (GGO), and the orangutan Pongo Pygmaeus (PPY). Human and both chimpanzees differed from gorilla and orangutan by the mapping of cos 170, a clone derived from chromosome 2cen-q11.2; the transposition of this orphon to the other side of the centromere can, therefore, be dated after the human/chimpanzee and gorilla divergence. Hybridization to homologous bands was also found with a cosmid clone containing a V{sub K}I orphon located on chromosome 1 (cos 115, main signal at 1q31-q32), although the probe is not fully unique. Also, a clone derived from the orphon V{sub K} region on chromosome 22q11 (cos 121) hybridized to the homologous bands in the great apes. This indicates that the orphons on human chromosomes 1 and 22 had been translocated early in primate evolution. 18 refs., 2 figs.

  5. INTRAVENOUS IMMUNOGLOBULIN IN PEDIATRIC RHEUMATOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    E. I. Alexeeva

    2015-01-01

    Full Text Available Modern successful treatment of rheumatic diseases is impossible without the use of intravenous immunoglobulin. The use of intravenous immunoglobulin is based on strict indications developed as a result of long-term multicenter controlled studies. The article highlights the issues of using immunoglobulin in pediatric rheumatology practice, and provides the review of literature with the results from the evaluation of the efficiency of intravenous immunoglobulin confirming the efficiency of the drug only for certain rheumatic diseases. 

  6. Immunoglobulin adsorption on modified surfaces

    NARCIS (Netherlands)

    Bremer, M.G.E.G.

    2001-01-01

    Preservation of biological functioning of proteins during immobilisation is of special interest in various biomedical and biotechnical applications. In industry physical adsorption of immunoglobulins (IgGs) onto solid surfaces is still the predominant immobilisation procedure because it is

  7. Hyper-immunoglobulin D syndrome with novel mutations in an afebrile infant.

    Science.gov (United States)

    Cadmus, Simi D; Green, Reid; Carrasco, Ruy; Levy, Moise L; Diaz, Lucia Z

    2018-03-30

    Hyper-immunoglobulin D syndrome is a rare autosomal-recessive autoinflammatory syndrome in which a mevalonate kinase deficiency results due to mutations of the mevalonate kinase gene. We report a case of an Asian male infant who was found to have hyper-immunoglobulin D syndrome in the absence of fever. His skin manifestations included cephalic pustulosis as well recurrent transient and fixed pink plaques and nodules on the face and extremities. Subsequent examination revealed hyper-immunoglobulin D syndrome with two novel allelic mutations in the mevalonate kinase gene: c.895G > A (p.D299N) and c.1168C > T (p.Q390). It is important for dermatologists to recognize the varied cutaneous presentations of hyper-immunoglobulin D syndrome because rapid diagnosis and treatment can significantly affect outcomes. © 2018 Wiley Periodicals, Inc.

  8. Radioimmunoassay to quantitatively measure cell surface immunoglobulins

    International Nuclear Information System (INIS)

    Krishman, E.C.; Jewell, W.R.

    1975-01-01

    A radioimmunoassay techniques developed to quantitatively measure the presence of immunoglobulins on the surface of cells, is described. The amount of immunoglobulins found on different tumor cells varied from 200 to 1140 ng/10 6 cells. Determination of immunoglobulins on the peripheral lymphocytes obtained from different cancer patients varied between 340 to 1040 ng/10 6 cells. Cultured tumor cells, on the other hand, were found to contain negligible quantities of human IgG [pt

  9. Detection of inflammatory lesions with radiolabelled immunoglobulins

    International Nuclear Information System (INIS)

    Blok, D.; Rijksuniversiteit Leiden; Ogtrop, M. van; Arndt, J.W.; Camps, J.A.J.; Feitsma, R.I.J.; Pauwels, E.K.J.

    1990-01-01

    Previous reports on the use of radiolabelled immunoglobulins led us to undertake a pilot experiment in an animal model to investigate the potentials sodium pertechnate Tc 99m-immunoglobulin scintigraphy in the detection of infectious foci. Mice infected in one leg with staphylococcus infection in were injected with sodium pertechnote Tc 99m-immunoglobulin, albumin aggregated technetium Tc 99m or gallium citrate Ga 67. The results obtained by scintigraphy suggested a specific accumulation of radiolabelled immunoglobulin at the site of infection. Visualization of the infection and the image quality, especially the 6- and 24-h images, were clearly enhanced after the use of immunoglobulin preparations as compared with those labelled with gallium. (orig.)

  10. Immunoglobulin heavy chain exclusion in the shark.

    Directory of Open Access Journals (Sweden)

    Karolina Malecek

    2008-06-01

    Full Text Available The adaptive immune system depends on specific antigen receptors, immunoglobulins (Ig in B lymphocytes and T cell receptors (TCR in T lymphocytes. Adaptive responses to immune challenge are based on the expression of a single species of antigen receptor per cell; and in B cells, this is mediated in part by allelic exclusion at the Ig heavy (H chain locus. How allelic exclusion is regulated is unclear; we considered that sharks, the oldest vertebrates possessing the Ig/TCR-based immune system, would yield insights not previously approachable and reveal the primordial basis of the regulation of allelic exclusion. Sharks have an IgH locus organization consisting of 15-200 independently rearranging miniloci (VH-D1-D2-JH-Cmu, a gene organization that is considered ancestral to the tetrapod and bony fish IgH locus. We found that rearrangement takes place only within a minilocus, and the recombining gene segments are assembled simultaneously and randomly. Only one or few H chain genes were fully rearranged in each shark B cell, whereas the other loci retained their germline configuration. In contrast, most IgH were partially rearranged in every thymocyte (developing T cell examined, but no IgH transcripts were detected. The distinction between B and T cells in their IgH configurations and transcription reveals a heretofore unsuspected chromatin state permissive for rearrangement in precursor lymphocytes, and suggests that controlled limitation of B cell lineage-specific factors mediate regulated rearrangement and allelic exclusion. This regulation may be shared by higher vertebrates in which additional mechanistic and regulatory elements have evolved with their structurally complex IgH locus.

  11. An inherited immunoglobulin class-switch recombination deficiency associated with a defect in the INO80 chromatin remodeling complex.

    Science.gov (United States)

    Kracker, Sven; Di Virgilio, Michela; Schwartzentruber, Jeremy; Cuenin, Cyrille; Forveille, Monique; Deau, Marie-Céline; McBride, Kevin M; Majewski, Jacek; Gazumyan, Anna; Seneviratne, Suranjith; Grimbacher, Bodo; Kutukculer, Necil; Herceg, Zdenko; Cavazzana, Marina; Jabado, Nada; Nussenzweig, Michel C; Fischer, Alain; Durandy, Anne

    2015-04-01

    Immunoglobulin class-switch recombination defects (CSR-D) are rare primary immunodeficiencies characterized by impaired production of switched immunoglobulin isotypes and normal or elevated IgM levels. They are caused by impaired T:B cooperation or intrinsic B cell defects. However, many immunoglobulin CSR-Ds are still undefined at the molecular level. This study's objective was to delineate new causes of immunoglobulin CSR-Ds and thus gain further insights into the process of immunoglobulin class-switch recombination (CSR). Exome sequencing in 2 immunoglobulin CSR-D patients identified variations in the INO80 gene. Functional experiments were performed to assess the function of INO80 on immunoglobulin CSR. We identified recessive, nonsynonymous coding variations in the INO80 gene in 2 patients affected by defective immunoglobulin CSR. Expression of wild-type INO80 in patients' fibroblastic cells corrected their hypersensitivity to high doses of γ-irradiation. In murine CH12-F3 cells, the INO80 complex accumulates at Sα and Eμ regions of the IgH locus, and downregulation of INO80 as well as its partners Reptin and Pontin impaired CSR. In addition, Reptin and Pontin were shown to interact with activation-induced cytidine deaminase. Finally, an abnormal separation of sister chromatids was observed upon INO80 downregulation in CH12-F3 cells, pinpointing its role in cohesin activity. INO80 deficiency appears to be associated with defective immunoglobulin CSR. We propose that the INO80 complex modulates cohesin function that may be required during immunoglobulin switch region synapsis. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Use of intravenous immunoglobulins in clinical practice

    Directory of Open Access Journals (Sweden)

    E.K. Donyush

    2011-01-01

    Full Text Available Immunoglobulins are main component of immune defense; they take part in anti-infectious resistance of organism and regulate processes of different immune reactions. Intravenous immunoglobulins are the most frequently used products made from donor blood plasma. The need in these drugs is steadily increasing during last 15–20 years, and indications are widening due to modern hightechnology methods of production and cleaning. The article presents modern data on formula, mechanisms of action and indications for different groups of intravenous immunoglobulins (standard, hyperimmune, fortified and description of possible adverse events.Key words: immuglobulines, prophylaxis, treatment, unfavorable reaction, children.

  13. Immunoglobulin kappa deleting element rearrangements in precursor-B acute lymphoblastic leukemia are stable targets for detection of minimal residual disease by real-time quantitative PCR

    NARCIS (Netherlands)

    van der Velden, V. H. J.; Willemse, M. J.; van der Schoot, C. E.; Hählen, K.; van Wering, E. R.; van Dongen, J. J. M.

    2002-01-01

    Immunoglobulin gene rearrangements are used as PCR targets for detection of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL). We Investigated the occurrence of monoclonal immunoglobulin kappa-deleting element (IGK-Kde) rearrangements by Southern blotting and PCR/heteroduplex

  14. Perspectives on Immunoglobulins in colostrum and milk

    DEFF Research Database (Denmark)

    Hurley, W L; Theil, Peter Kappel

    2011-01-01

    Immunoglobulins form an important component of the immunological activity found in milk and colostrum. They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring. The mechanism of transfer varies among mammalian species. Cattle provide...... a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans. Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases....... The use of colostrum or milk as a source of immunoglobulins, whether intended for the neonate of the species producing the secretion or for a different species, can be viewed in the context of the types of immunoglobulins in the secretion, the mechanisms by which the immunoglobulins are secreted...

  15. Immunoglobulin superfamily members encoded by viruses and their multiple roles in immune evasion.

    Science.gov (United States)

    Farré, Domènec; Martínez-Vicente, Pablo; Engel, Pablo; Angulo, Ana

    2017-05-01

    Pathogens have developed a plethora of strategies to undermine host immune defenses in order to guarantee their survival. For large DNA viruses, these immune evasion mechanisms frequently rely on the expression of genes acquired from host genomes. Horizontally transferred genes include members of the immunoglobulin superfamily, whose products constitute the most diverse group of proteins of vertebrate genomes. Their promiscuous immunoglobulin domains, which comprise the building blocks of these molecules, are involved in a large variety of functions mediated by ligand-binding interactions. The flexible structural nature of the immunoglobulin domains makes them appealing targets for viral capture due to their capacity to generate high functional diversity. Here, we present an up-to-date review of immunoglobulin superfamily gene homologs encoded by herpesviruses, poxviruses, and adenoviruses, that include CD200, CD47, Fc receptors, interleukin-1 receptor 2, interleukin-18 binding protein, CD80, carcinoembryonic antigen-related cell adhesion molecules, and signaling lymphocyte activation molecules. We discuss their distinct structural attributes, binding properties, and functions, shaped by evolutionary pressures to disarm specific immune pathways. We include several novel genes identified from extensive genome database surveys. An understanding of the properties and modes of action of these viral proteins may guide the development of novel immune-modulatory therapeutic tools. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Spatial and temporal expression of immunoglobulin superfamily member 1 in the rat

    NARCIS (Netherlands)

    Joustra, Sjoerd D.; Meijer, Onno C.; Heinen, Charlotte A.; Mol, Isabel M.; Laghmani, El Houari; Sengers, Rozemarijn M. A.; Carreno, Gabriela; van Trotsenburg, A. S. Paul; Biermasz, Nienke R.; Bernard, Daniel J.; Wit, Jan M.; Oostdijk, Wilma; van Pelt, Ans M. M.; Hamer, Geert; Wagenaar, Gerry T. M.

    2015-01-01

    Loss-of-function mutations in the immunoglobulin superfamily member 1 (IGSF1) gene cause an X-linked syndrome of central hypothyroidism, macroorchidism, variable prolactin and GH deficiency, delayed pubertal testosterone rise, and obesity. To understand the pathophysiology of this syndrome,

  17. Immunoglobulin E-Mediated Autoimmunity

    Directory of Open Access Journals (Sweden)

    Marcus Maurer

    2018-04-01

    Full Text Available The study of autoimmunity mediated by immunoglobulin E (IgE autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP, and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves’ disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them.

  18. Immunoglobulin Genomics in the Guinea Pig (Cavia porcellus)

    Science.gov (United States)

    Guo, Yongchen; Bao, Yonghua; Meng, Qingwen; Hu, Xiaoxiang; Meng, Qingyong; Ren, Liming; Li, Ning; Zhao, Yaofeng

    2012-01-01

    In science, the guinea pig is known as one of the gold standards for modeling human disease. It is especially important as a molecular and cellular biology model for studying the human immune system, as its immunological genes are more similar to human genes than are those of mice. The utility of the guinea pig as a model organism can be further enhanced by further characterization of the genes encoding components of the immune system. Here, we report the genomic organization of the guinea pig immunoglobulin (Ig) heavy and light chain genes. The guinea pig IgH locus is located in genomic scaffolds 54 and 75, and spans approximately 6,480 kb. 507 VH segments (94 potentially functional genes and 413 pseudogenes), 41 DH segments, six JH segments, four constant region genes (μ, γ, ε, and α), and one reverse δ remnant fragment were identified within the two scaffolds. Many VH pseudogenes were found within the guinea pig, and likely constituted a potential donor pool for gene conversion during evolution. The Igκ locus mapped to a 4,029 kb region of scaffold 37 and 24 is composed of 349 Vκ (111 potentially functional genes and 238 pseudogenes), three Jκ and one Cκ genes. The Igλ locus spans 1,642 kb in scaffold 4 and consists of 142 Vλ (58 potentially functional genes and 84 pseudogenes) and 11 Jλ -Cλ clusters. Phylogenetic analysis suggested the guinea pig’s large germline VH gene segments appear to form limited gene families. Therefore, this species may generate antibody diversity via a gene conversion-like mechanism associated with its pseudogene reserves. PMID:22761756

  19. Killer Cell Immunoglobulin-like Receptors and their Ligands

    Directory of Open Access Journals (Sweden)

    Tajik N.

    2010-09-01

    Full Text Available The Natural killer (NK cells are a subset of lymphocytes comprising around 10% of total lymphocytes in peripheral blood. Due to their role in the innate response, NK cells provide a ‘first line of defense’ against infectious agents and cancer and are also thought to play a role in autoimmunity. The killer cell immunoglobulin-like receptors (KIR are regulatory surface molecules, found on NK cells and on a subset of T lymphocytes. The genes for KIR are present on chromosome 19 in the leukocyte receptor complex and show a major difference for both the type and number of KIR genes present among different ethnic groups. They have been divided into two groups of 2D or 3D, depending on the number of external immunoglobulin domains. The presence of a long cytoplasmic tail with two immune tyrosine-based inhibitory motifs (ITIM allows the transduction of inhibitory signals and characterizes the inhibitory KIRs (2DL and 3DL, whereas the presence of short cytoplasmic tails corresponds to the activating KIR receptors (2DS and 3DS.These polymorphic receptors interact with specific motifs on human leukocyte antigen (HLA class I molecules, modulate NK cytolytic activity. Some KIRs are known to interact with HLA-C molecules of target cells, HLA-Bw4 molecules and HLA-A3/11. For some KIRs the corresponding ligands are still unknown.

  20. The normally expressed kappa immunoglobulin light chain gene repertoire and somatic mutations studied by single-sided specific polymerase chain reaction (PCR); frequent occurrence of features often assigned to autoimmunity

    DEFF Research Database (Denmark)

    Juul, L; Hougs, L; Andersen, V

    1997-01-01

    The expressed human kappa light chain gene repertoire utilized by healthy individuals was studied by two different single-sided specific PCR techniques to avoid bias for certain V genes. A total of 103 rearranged kappa sequences from peripheral blood mononuclear cells from healthy individuals were...

  1. WPMSD: A Malicious Script Detection Method Inspired by the Process of Immunoglobulin Secretion

    Directory of Open Access Journals (Sweden)

    Hui Zhao

    2011-10-01

    Full Text Available Inspired by the process of immunoglobulin secretion in biological body, we present a Web Page Malicious Script Detection Method (WPMSD. In this paper, Firstly, the basic definitions of artificial immune items are given. Secondly, according to the spreading range of malicious script, the immunoglobulin number is changed as the detector clone proliferation is stimulated by malicious scripts. Further more, the nonlinear dynamics of antibody number is discussed. Thirdly, we propose a probability approach to trigger alarms to inform that the detected scripts are harmful. Finally, the WPMSD collects the effective immunoglobulin set based on Hidden Markov Model (HMM to update the detector gene library. Compared with the traditional immune based detection methods, such as Negative Selection Algorithm (NSA, Dynamic Colonel Selection (DynamiCS, and Variable size Detector (Vdetector, the false alarm rate of WPMSD has been reduced by 18.09%, 12.6%, and 7.47% respectively.

  2. A novel IgA-like immunoglobulin in the reptile Eublepharis macularius.

    Science.gov (United States)

    Deza, Francisco Gambón; Espinel, Christian Sánchez; Beneitez, Julio Valdueza

    2007-01-01

    The appearance of antibody genes over evolution coincided with the origin of the vertebrates. Reptiles are of great interest in evolution since they are the link between the amphibians, birds, and mammals. This work describes the presence of a gene in the reptile leopard gecko (Eublepharis macularius) where phylogenetic studies suggest that it is the gene orthologue of immunoglobulin A (IgA) and immunoglobulin X (IgX) in Xenopus. Messenger RNA samples taken from different tissues showed expression of this antibody in intestinal tissue. Data on the structure deduced from the sequence of nucleotides showed an antibody with four domains in the constant region. There is a sequence of 20 amino acids in the C terminus similar to the secretory tail of immunoglobulin M (IgM) and IgA. A detailed analysis of the sequence of amino acids displayed a paradox, i.e., domains CH1 and CH2 showed a clear homology with domains CH1 and CH2 of immunoglobulin Y (IgY) while domains CH3 and CH4 were homologous with domains CH3 and CH4 of IgM. This homology pattern is also seen in Xenopus IgX and bird IgA. The most logical explanation for this phenomenon is that a recombination between the IgM and IgY gave rise to the IgA.

  3. Enhancement of polymeric immunoglobulin receptor transcytosis by biparatopic VHH.

    Directory of Open Access Journals (Sweden)

    Chris D Emmerson

    Full Text Available The polymeric immunoglobulin receptor (pIgR ensures the transport of dimeric immunoglobulin A (dIgA and pentameric immunoglobulin M (pIgM across epithelia to the mucosal layer of for example the intestines and the lungs via transcytosis. Per day the human pIgR mediates the excretion of 2 to 5 grams of dIgA into the mucosa of luminal organs. This system could prove useful for therapies aiming at excretion of compounds into the mucosa. Here we investigated the use of the variable domain of camelid derived heavy chain only antibodies, also known as VHHs or Nanobodies®, targeting the human pIgR, as a transport system across epithelial cells. We show that VHHs directed against the human pIgR are able to bind the receptor with high affinity (∼1 nM and that they compete with the natural ligand, dIgA. In a transcytosis assay both native and phage-bound VHH were only able to get across polarized MDCK cells that express the human pIgR gene in a basolateral to apical fashion. Indicating that the VHHs are able to translocate across epithelia and to take along large particles of cargo. Furthermore, by making multivalent VHHs we were able to enhance the transport of the compounds both in a MDCK-hpIgR and Caco-2 cell system, probably by inducing receptor clustering. These results show that VHHs can be used as a carrier system to exploit the human pIgR transcytotic system and that multivalent compounds are able to significantly enhance the transport across epithelial monolayers.

  4. Translocations affecting human immunoglobulin heavy chain locus

    Directory of Open Access Journals (Sweden)

    Sklyar I. V.

    2014-03-01

    Full Text Available Translocations involving human immunoglobulin heavy chain (IGH locus are implicated in different leukaemias and lymphomas, including multiple myeloma, mantle cell lymphoma, Burkitt’s lymphoma and diffuse large B cell lymphoma. We have analysed published data and identified eleven breakpoint cluster regions (bcr related to these cancers within the IgH locus. These ~1 kbp bcrs are specific for one or several types of blood cancer. Our findings could help devise PCR-based assays to detect cancer-related translocations, to identify the mechanisms of translocations and to help in the research of potential translocation partners of the immunoglobulin locus at different stages of B-cell differentiation.

  5. Facilitated subcutaneous immunoglobulin administration (fSCIg)

    DEFF Research Database (Denmark)

    Blau, Igor-Wolfgang; Conlon, Niall; Petermann, Robert

    2016-01-01

    and diverse medical needs that treatments for SID management should strive to meet. In this special report, we study the opportunities provided by facilitated subcutaneous immunoglobulin administration (fSCIg) to treat patients for whom the conventional routes (intravenous and subcutaneous) are sub...

  6. Ancient Phylogenetic Beginnings of Immunoglobulin Hypermutation

    Czech Academy of Sciences Publication Activity Database

    Kubrycht, J.; Sigler, Karel; Růžička, Michal; Souček, P.; Borecký, J.; Ježek, Petr

    2006-01-01

    Roč. 63, - (2006), s. 691-706 ISSN 0022-2844 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z50110509 Keywords : immunoglobulin * hypermutation * antigen Subject RIV: EE - Microbiology, Virology Impact factor: 2.767, year: 2006

  7. The Immunobiology of Immunoglobulin G4

    NARCIS (Netherlands)

    Lighaam, Laura C.; Rispens, Theo

    2016-01-01

    Human immunoglobulin G4 (IgG4) antibodies are in many ways unusual. In this review, an overview is given of the structural and functional aspects of IgG4 antibodies, the consequences of IgG4 antibody formation in various disease settings, and the factors involved in the regulation of IgG4 responses.

  8. Immunoglobulins and their fragments on solid surfaces

    NARCIS (Netherlands)

    Buijs, J.A.G.

    1995-01-01

    Summary

    Adsorption of immunoglobulin G (IgG) is a common step in the production of immunological tests and biosensors. The use of IgG in these applications stems from its ability to specifically bind all kinds of molecules (antigens). In these tests the IgG

  9. Ikaros controls isotype selection during immunoglobulin class switch recombination.

    Science.gov (United States)

    Sellars, MacLean; Reina-San-Martin, Bernardo; Kastner, Philippe; Chan, Susan

    2009-05-11

    Class switch recombination (CSR) allows the humoral immune response to exploit different effector pathways through specific secondary antibody isotypes. However, the molecular mechanisms and factors that control immunoglobulin (Ig) isotype choice for CSR are unclear. We report that deficiency for the Ikaros transcription factor results in increased and ectopic CSR to IgG(2b) and IgG(2a), and reduced CSR to all other isotypes, regardless of stimulation. Ikaros suppresses active chromatin marks, transcription, and activation-induced cytidine deaminase (AID) accessibility at the gamma2b and gamma2a genes to inhibit class switching to these isotypes. Further, Ikaros directly regulates isotype gene transcription as it directly binds the Igh 3' enhancer and interacts with isotype gene promoters. Finally, Ikaros-mediated repression of gamma2b and gamma2a transcription promotes switching to other isotype genes by allowing them to compete for AID-mediated recombination at the single-cell level. Thus, our results reveal transcriptional competition between constant region genes in individual cells to be a critical and general mechanism for isotype specification during CSR. We show that Ikaros is a master regulator of this competition.

  10. Limited number of immunoglobulin VH regions expressed in the mutant rabbit "Alicia".

    Science.gov (United States)

    DiPietro, L A; Short, J A; Zhai, S K; Kelus, A S; Meier, D; Knight, K L

    1990-06-01

    A unique feature of rabbit Ig is the presence of VH region allotypic specificities. In normal rabbits, more than 80% of circulating immunoglobulin molecules bear the VHa allotypic specificities, al, a2 or a3; the remaining 10% to 20% of immunoglobulin molecules lack VHa allotypic specificities and are designated VHa-. A mutant rabbit designated Alicia, in contrast, has predominantly serum immunoglobulin molecules that lack the VHa allotypic specificities (Kelus and Weiss, Proc. Natl. Acad. Sci. USA 1986. 83: 4883). To study the nature and molecular complexity of VHa- molecules, we cloned and determined the nucleotide sequence of seven cDNA prepared from splenic RNA of an Alicia rabbit. Six of the clones appeared to encode VHa- molecules; the framework regions encoded by these clones were remarkably similar to each other, each having an unusual insertion of four amino acids at position 10. This insertion of four amino acids has been seen in only 2 of 54 sequenced rabbit VH genes. The similarity of the sequences of the six VHa- clones to each other and their dissimilarity to most other VH genes leads us to suggest that the VHa- molecules in Alicia rabbits are derived predominantly from one or a small number of very similar VH genes. Such preferential utilization of a small number of VH genes may explain the allelic inheritance of VH allotypes.

  11. Camelid immunoglobulins and nanobody technology.

    Science.gov (United States)

    Muyldermans, S; Baral, T N; Retamozzo, V Cortez; De Baetselier, P; De Genst, E; Kinne, J; Leonhardt, H; Magez, S; Nguyen, V K; Revets, H; Rothbauer, U; Stijlemans, B; Tillib, S; Wernery, U; Wyns, L; Hassanzadeh-Ghassabeh, Gh; Saerens, D

    2009-03-15

    It is well established that all camelids have unique antibodies circulating in their blood. Unlike antibodies from other species, these special antibodies are devoid of light chains and are composed of a heavy-chain homodimer. These so-called heavy-chain antibodies (HCAbs) are expressed after a V-D-J rearrangement and require dedicated constant gamma-genes. An immune response is raised in these so-called heavy-chain antibodies following classical immunization protocols. These HCAbs are easily purified from serum, and the antigen-binding fragment interacts with parts of the target that are less antigenic to conventional antibodies. Since the antigen-binding site of the dromedary HCAb is comprised in one single domain, referred to as variable domain of heavy chain of HCAb (VHH) or nanobody (Nb), we designed a strategy to clone the Nb repertoire of an immunized dromedary and to select the Nbs with specificity for our target antigens. The monoclonal Nbs are well produced in bacteria, are very stable and highly soluble, and bind their cognate antigen with high affinity and specificity. We have successfully developed recombinant Nbs for research purposes, as probe in biosensors, to diagnose infections, and to treat diseases like cancer or trypanosomosis.

  12. Intravenous immunoglobulin and Alzheimer's disease immunotherapy.

    Science.gov (United States)

    Solomon, Beka

    2007-02-01

    Amyloid-beta peptide (Abeta) contributes to the acute progression of Alzheimer's disease (AD) and has become the main target for therapeutics. Active immunization with Abeta in individuals with AD has been efficacious; however, some patients developed side effects, possibly related to an autoimmune response. Evidence that intravenous immunoglobulin (IVIg), an FDA-approved purified immunoglobulin fraction from normal human donor blood, shows promise of passive immunotherapy for AD is reviewed. Investigations into the molecular effects of IVIg on Abeta clearance, using the BV-2 cellular microglia line, demonstrate that IVIg dissolves Abeta fibrils in vitro, increases cellular tolerance to Abeta, enhances microglial migration toward Abeta deposits, and mediates phagocytosis of Abeta. Preliminary clinical results indicate that IVIg, which contains natural antibodies against the Abeta, warrants further study into its potential to deliver a controlled immune attack on the peptide, avoiding the immune toxicities that have had a negative impact on the first clinical trials of vaccine against Abeta.

  13. Neuromyelitis Optica Immunoglobulin G in a Child

    OpenAIRE

    Hudson, Lynsee A.; Bernard, Timothy J.; Tseng, Brian S.; Miller, Bradford R.; Corboy, John R.

    2006-01-01

    Neuromyelitis optica or Devic’s syndrome is an uncommon demyelinating disorder that preferentially attacks the spinal cord and optic nerves. Although it is well described in adults, childhood neuromyelitis optica has rarely been reported in the literature and is frequently misdiagnosed as severe multiple sclerosis. Recently, a serum immunoglobulin G test for neuromyelitis optica has become available which may clarify and accelerate the diagnosis. This report describes a child with recurrent m...

  14. IMGT unique numbering for immunoglobulin and T cell receptor constant domains and Ig superfamily C-like domains

    DEFF Research Database (Denmark)

    Lefranc, Marie-Paule; Pommié, Christelle; Kaas, Quentin

    2005-01-01

    IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr) provides a common access to expertly annotated data on the genome, proteome, genetics and structure of immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC), and related proteins...

  15. Hydrometer test for estimation of immunoglobulin concentration in bovine colostrum.

    Science.gov (United States)

    Fleenor, W A; Stott, G H

    1980-06-01

    A practical field method for measuring immunoglobulin concentration in bovine colostrum has been developed from the linear relationship between colostral specific gravity and immunoglobulin concentration. Fourteen colostrums were collected within 24 h postpartum from nursed and unnursed cows and were assayed for specific gravity and major colostral constituents. Additionally, 15 colostrums were collected immediately postpartum prior to suckling and assayed for specific gravity and immunoglobulin concentration. Regression analysis provided an equation to estimate colostral immunoglobulin concentration from the specific gravity of fresh whole colostrum. From this, a colostrometer was developed for practical field use.

  16. Screening for congenital toxoplasmosis: accuracy of immunoglobulin M and immunoglobulin A tests after birth

    DEFF Research Database (Denmark)

    Gilbert, Ruth E; Thalib, Lukman; Tan, Hooi Kuan

    2007-01-01

    OBJECTIVES: To determine the accuracy of postnatal screening for toxoplasma-specific immunoglobulin (Ig) M and IgA. SETTING: Ten centres in three European countries. METHODS: We compared results of the first postnatal IgM or IgA test in infants with infected mothers identified by prenatal screeni...

  17. Immunoglobulin therapy for enteroviral meningitides in children

    Directory of Open Access Journals (Sweden)

    O. G. Kimirilova

    2016-01-01

    Full Text Available The authors give the material of their own observations on the clinical and laboratory efficacy of the Russian intravenous immunoglobulin Gabriglobin for the treatment of enteroviral meningitides in children.The performed trials indicated that the use of Gabriglobin in the combination therapy of severe enteroviral meningitides in children reduced the duration of intoxication, global cerebral symptoms, meningeal syndrome, the time of cerebrospinal fluid sanitation by 1,5 times, and that of in-hospital treatment by 5,8±1,8 days as compared to those who received conventional basic therapy.

  18. Serology and immunoglobulin profile in rheumatoid arthritis.

    Science.gov (United States)

    Adhya, S; Chakraborty, G; Hajra, B; Bhattacharya, S; Sikdar, P K; Sinha, S; Banerjee, P P; Ghosh, E; Chakraborty, P

    1998-01-01

    One hundred and twenty cases of clinically diagnosed rheumatoid arthritis, 80 non-rheumatoid cases suffering from various other diseases and 40 healthy individuals were investigated for the presence of rheumatoid factor, quantitation of serum immunoglobulin, demonstration of ANA and LE cell phenomenon. Microlatex agglutination test of serum for rheumatoid factor showed 56.6% positivity in rheumatoid group and 3.7% positivity in non-rheumatoid group. All three serum immunoglobulins (IgG, IgM, IgA) were raised in serum in significant titre in cases of rheumatoid arthritis, whereas only IgA lever was elevated in the group of non-rheumatoid diseases. ANA and LE cell phenomenon were observed in 11.7% and 4.4% cases of rheumatoid arthritis who had severe underlying disease. In non-rheumatoid group, only one of 6 cases of systemic lupus erythematosus showed rheumatoid factor and that too in an insignificant titre (less than 1:20). Synovium and synovial fluid contained plenty of plasma cells and lymphocytes. It has been observed that RF appears first in synovial fluid and it may take several months to a year to attain detectable level in serum.

  19. Intravenous immunoglobulin therapy and systemic lupus erythematosus.

    Science.gov (United States)

    Zandman-Goddard, Gisele; Levy, Yair; Shoenfeld, Yehuda

    2005-12-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.

  20. Mutation Pattern of Paired Immunoglobulin Heavy and Light Variable Domains in Chronic Lymphocytic Leukemia B Cells

    Science.gov (United States)

    Ghiotto, Fabio; Marcatili, Paolo; Tenca, Claudya; Calevo, Maria Grazia; Yan, Xiao-Jie; Albesiano, Emilia; Bagnara, Davide; Colombo, Monica; Cutrona, Giovanna; Chu, Charles C; Morabito, Fortunato; Bruno, Silvia; Ferrarini, Manlio; Tramontano, Anna; Fais, Franco; Chiorazzi, Nicholas

    2011-01-01

    B-cell chronic lymphocytic leukemia (CLL) patients display leukemic clones bearing either germline or somatically mutated immunoglobulin heavy variable (IGHV ) genes. Most information on CLL immunoglobulins (Igs), such as the definition of stereotyped B-cell receptors (BCRs), was derived from germline unmutated Igs. In particular, detailed studies on the distribution and nature of mutations in paired heavy- and light-chain domains of CLL clones bearing mutated Igs are lacking. To address the somatic hyper-mutation dynamics of CLL Igs, we analyzed the mutation pattern of paired IGHV–diversity-joining (IGHV-D-J ) and immunoglobulin kappa/lambda variable-joining (IGK/LV-J ) rearrangements of 193 leukemic clones that displayed ≥2% mutations in at least one of the two immunoglobulin variable (IGV ) genes (IGHV and/or IGK/LV ). The relationship between the mutation frequency in IGHV and IGK/LV complementarity determining regions (CDRs) and framework regions (FRs) was evaluated by correlation analysis. Replacement (R) mutation frequency within IGK/LV chain CDRs correlated significantly with mutation frequency of paired IGHV CDRs in λ but not κ isotype CLL clones. CDRs of IGKV-J rearrangements displayed a lower percentage of R mutations than IGHVs. The frequency/pattern of mutations in kappa CLL Igs differed also from that in κ-expressing normal B cells described in the literature. Instead, the mutation frequency within the FRs of IGHV and either IGKV or IGLV was correlated. Notably, the amount of diversity introduced by replaced amino acids was comparable between IGHVs and IGKVs. The data indicate a different mutation pattern between κ and λ isotype CLL clones and suggest an antigenic selection that, in κ samples, operates against CDR variation. PMID:21785810

  1. Mutation Pattern of Paired Immunoglobulin Heavy and Light Variable Domains in Chronic Lymphocytic Leukemia B Cells

    KAUST Repository

    Ghiotto, Fabio; Marcatili, Paolo

    2011-01-01

    B-cell chronic lymphocytic leukemia (CLL) patients display leukemic clones bearing either germline or somatically mutated immunoglobulin heavy variable (IGHV ) genes. Most information on CLL immunoglobulins (Igs), such as the definition of stereotyped B-cell receptors (BCRs), was derived from germline unmutated Igs. In particular, detailed studies on the distribution and nature of mutations in paired heavy- and light-chain domains of CLL clones bearing mutated Igs are lacking. To address the somatic hyper-mutation dynamics of CLL Igs, we analyzed the mutation pattern of paired IGHV-diversity-joining (IGHV-D-J ) and immunoglobulin kappa/lambda variable-joining (IGK/LV-J ) rearrangements of 193 leukemic clones that displayed ≥ 2% mutations in at least one of the two immunoglobulin variable (IGV ) genes (IGHV and/or IGK/LV ). The relationship between the mutation frequency in IGHV and IGK/LV complementarity determining regions (CDRs) and framework regions (FRs) was evaluated by correlation analysis. Replacement (R) mutation frequency within IGK/LV chain CDRs correlated significantly with mutation frequency of paired IGHV CDRs in λ but not κ isotype CLL clones. CDRs of IGKV-J rearrangements displayed a lower percentage of R mutations than IGHVs. The frequency/pattern of mutations in kappa CLL Igs differed also from that in κ-expressing normal B cells described in the literature. Instead, the mutation frequency within the FRs of IGHV and either IGKV or IGLV was correlated. Notably, the amount of diversity introduced by replaced amino acids was comparable between IGHVs and IGKVs. The data indicate a different mutation pattern between κ and λ isotype CLL clones and suggest an antigenic selection that, in κ samples, operates against CDR variation.

  2. Levels of serum immunoglobulins in apparently healthy children and ...

    African Journals Online (AJOL)

    The results also confirm suggestions that levels of some immunoglobulin types seen amongst African adults may have possibly been attained during childhood. Our study could be of value since previous reports in this regard have been relatively scanty especially in this part of Nigeria. Keywords: Immunoglobulin, Immunity ...

  3. Levels of serum immunoglobulins in apparently healthy children and ...

    African Journals Online (AJOL)

    olayemitoyin

    suggestions that levels of some immunoglobulin types seen amongst African adults may have possibly been attained during childhood. Our study could be of value since previous reports in this regard have been relatively scanty especially in this part of Nigeria. Keywords: Immunoglobulin, Immunity, IgA, IgG, IgM.

  4. Immunoglobulin Concentration in Tears of Contact Lens Wearers

    Directory of Open Access Journals (Sweden)

    Rajendra P Maurya

    2014-01-01

    Conclusion: The relation of immunoglobulin concentration with increasing duration of wear and material of contact lens shows that tear immunoglobulin rise accrues due to mechanical stimulation, hence contact lenses should not be used for a long period and lenses of hard nature should be discouraged. The maintenance, cleaning and deproteinization of the lenses are of high importance to avoid immunostimulation.

  5. INTERACTION OF ALBUMIN AND IMMUNOGLOBULIN G WITH SYNTHETIC HYDROXYAPATITE

    Directory of Open Access Journals (Sweden)

    E. Pylypchuk

    2012-12-01

    Full Text Available It was shown by X-ray phase analysis, IR spectra analysis and MALDI-ToF mass spectrometry methods that interaction of synthetic hydroxyapatite with a solution of immunoglobulin G leads to its partial dissolution due to leaching from the surface of calcium triphosphate which, in our opinion, forms complexes with immunoglobulin G.

  6. Solar urticaria successfully treated with intravenous immunoglobulin.

    LENUS (Irish Health Repository)

    Hughes, R

    2012-02-01

    Idiopathic solar urticaria (SU) is a rare, debilitating photodermatosis, which may be difficult to treat. First-line treatment with antihistamines is effective in mild cases, but remission after phototherapeutic induction of tolerance is often short-lived. Other treatment options include plasma exchange, photopheresis and cyclosporin. We present two cases of severe, idiopathic SU, which were resistant to conventional treatment. Both patients achieved remission after administration of intravenous immunoglobulin (IVIg) and have remained in remission at 13 months and 4 years, respectively. There are only two case reports of successful treatment of solar urticaria with IVIg. In our experience IVIg given at a total dose of 2 g\\/kg over several 5-day courses about a month apart is an effective treatment option for severe idiopathic SU. It is also generally safe, even if certainly subject to significant theoretical risks, such as induction of viral infection or anaphylaxis.

  7. Immunoglobulin G4-Related Disease: An Update

    Directory of Open Access Journals (Sweden)

    Abdullah Al-Mujaini

    2018-03-01

    Full Text Available Immunoglobulin G4-related disease (IgG4-RD is an increasingly recognized immune-mediated condition comprised of a collection of disorders that share specific pathological, serological, and clinical features. IgG4-RD is a fibroinflammatory condition with a tendency to form tumors with inflammatory infiltrate with IgG4 rich plasma cells and elevation of serum IgG4, which may affect virtually every organ and tissue. IgG4-related ophthalmic disease may present as dacryoadenitis, myositis, or involvement of other orbital tissue. Hypophysitis or pachymeningitis may manifest as cranial neuropathies. The diagnosis of IgG4-RD is based on a typical clinical scenario, supportive laboratory test, expected radiological characteristics, and distinct histopathological and immunohistochemical features. Corticosteroids and immunosuppressives form the mainline treatment.

  8. Structural repertoire of immunoglobulin λ light chains

    KAUST Repository

    Chailyan, Anna

    2011-03-01

    The immunoglobulin λ isotype is present in nearly all vertebrates and plays an important role in the human immune system. Despite its importance, few systematic studies have been performed to analyze the structural conformation of its variable regions, contrary to what is the case for κ and heavy chains. We show here that an analysis of the structures of λ chains allows the definition of a discrete set of recurring conformations (canonical structures) of their hypervariable loops and, most importantly, the identification of sequence constraints that can be used to predict their structure. We also show that the structural repertoire of λ chains is different and more varied than that of the κ chains, consistently with the current view of the involvement of the two major light-chain families in complementary strategies of the immune system to ensure a fine tuning between diversity and stability in antigen recognition. © 2011 Wiley-Liss, Inc.

  9. Structural repertoire of immunoglobulin λ light chains

    KAUST Repository

    Chailyan, Anna; Marcatili, Paolo; Cirillo, Davide; Tramontano, Anna

    2011-01-01

    The immunoglobulin λ isotype is present in nearly all vertebrates and plays an important role in the human immune system. Despite its importance, few systematic studies have been performed to analyze the structural conformation of its variable regions, contrary to what is the case for κ and heavy chains. We show here that an analysis of the structures of λ chains allows the definition of a discrete set of recurring conformations (canonical structures) of their hypervariable loops and, most importantly, the identification of sequence constraints that can be used to predict their structure. We also show that the structural repertoire of λ chains is different and more varied than that of the κ chains, consistently with the current view of the involvement of the two major light-chain families in complementary strategies of the immune system to ensure a fine tuning between diversity and stability in antigen recognition. © 2011 Wiley-Liss, Inc.

  10. Physical map and one-megabase sequencing of the human immunoglobulin lambda locus

    Directory of Open Access Journals (Sweden)

    Geraldo A.S. Passos Jr.

    1998-06-01

    Full Text Available The human immunoglobulin lambda (IGL locus is located on chromosome 22q11.1-q11.2 and contains the genes responsible for the immunoglobulin lambda light chains. This locus was recently mapped (physical map and its 1-Mb DNA totally sequenced. In this review we focus on the characterization of the v-lambda genes, its chromosomal location, genomics and sequencing of the IGL locus.O locus IGL humano está localizado no cromosomo 22q11.1-q11.2 e contém os genes responsáveis pelas cadeias leves de imunoglobulina tipo lambda. Este locus foi recentemente mapeado (mapa físico e seu 1 Mb DNA totalmente sequenciado. Nesta revisão focamos os principais resultados de caracterização dos genes v-lambda, sua localização cromossômica, a genômica e seqüenciamento do locus IGL.

  11. Acute Inflammatory Demyelinating Neuropathy : Immunoglobulin And Immune Complex Profile

    Directory of Open Access Journals (Sweden)

    Shripad A

    2003-01-01

    Full Text Available Serum immunoglobulins (IgG, IgA and IgM and immune complexes IgG (IcG were measured in 58 cases of acute inflammatory demyelinating neuropathy, popularly known as Guillian Barre′ syndrome, and in 30 healthy controls using single radial immunodiffusion assay. Immunoglobulin and immune complex levels were significantly elevated in patients as compared to controls. The increased levels of immunoglobulins and immune complexes may contribute to the pathogenesis of the disease and provide rationale for therapeutic plasmapheresis.

  12. HETEROGENEITY OF POLYCLONAL IMMUNOGLOBULINS NUCLEASE ACTIVITY IN RHEUMATOID AND REACTIVE ARTHRITIS

    Directory of Open Access Journals (Sweden)

    M. V. Volkova

    2017-01-01

    Full Text Available Catalytic properties of immunoglobulins are widely studied within recent years. It was found that nuclease activity of immunoglobulins is increased in systemic autoimmune diseases. Given some pathogenetic features of rheumatoid arthritis and reactive arthritis, it is appropriate to clarify the nature of nuclease activity in these diseases. Determination of DNAse activity of immunoglobulins with different DNA substrates, and search for specific substrates for distinct clinical entities could serve these purposes. The aim of present work is to determine DNase activity of the polyclonal class G immunoglobulins in rheumatoid and reactive arthritis using various methods.Different methods are used to evaluate nuclease activity. In this paper we present newly developed and modified techniques for determination of DNAse activity of polyclonal IgGs. Particular attention was paid to the electrophoretic method of DNase activity assessment. Polyclonal IgG isolated from blood serum of patients with rheumatoid arthritis and reactive arthritis were used for assays. In this study, we demonstrated the presence of an inhomogeneous DNase activity of immunoglobulins in relation to different substrates.Along with calf thymus DNA, we used bacterial plasmid DNA and PCR products based on bacterial gene sequences. Levels of DNase activity by rivanol clot method with calf thymus DNA as substrate proved to be higher in patients with rheumatoid arthritis than the control values (p < 0.01. DNase abzyme activity in patients with rheumatoid arthritis was elevated, as compared to the patients with reactive arthritis (p < 0.01.When examining ability of the IgG to hydrolyze procaryotic DNA (bacterial plasmid DNA and PCR products, based on bacterial genes, we obtained heterogeneous results. Different Ig samples showed varying degrees of DNA hydrolysis. Abzyme hydrolysis of DNA substrates longer than 700 bp was more pronounced, as compared to short DNA substrates (100 base pairs

  13. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  14. Immunoglobulin for alloimmune hemolytic disease in neonates.

    Science.gov (United States)

    Zwiers, Carolien; Scheffer-Rath, Mirjam Ea; Lopriore, Enrico; de Haas, Masja; Liley, Helen G

    2018-03-18

    Exchange transfusion and phototherapy have traditionally been used to treat jaundice and avoid the associated neurological complications. Because of the risks and burdens of exchange transfusion, intravenous immunoglobulin (IVIg) has been suggested as an alternative therapy for alloimmune hemolytic disease of the newborn (HDN) to reduce the need for exchange transfusion. To assess the effect and complications of IVIg in newborn infants with alloimmune HDN on the need for and number of exchange transfusions. We performed electronic searches of CENTRAL, PubMed, Embase (Ovid), Web of Science, CINAHL (EBSCOhost), Academic Search Premier, and the trial registers ClinicalTrials.gov and controlled-trials.com in May 2017. We also searched reference lists of included and excluded trials and relevant reviews for further relevant studies. We considered all randomized and quasi-randomized controlled trials of IVIg in the treatment of alloimmune HDN. Trials must have used predefined criteria for the use of IVIg and exchange transfusion therapy to be included. We used the standard methods of Cochrane and its Neonatal Review Group. We assessed studies for inclusion and two review authors independently assessed quality and extracted data. We discussed any differences of opinion to reach consensus. We contacted investigators for additional or missing information. We calculated risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) for categorical outcomes. We calculated mean difference (MD) for continuous variables. We used GRADE criteria to assess the risk of bias for major outcomes and to summarize the level of evidence. Nine studies with 658 infants fulfilled the inclusion criteria. Term and preterm infants with Rh or ABO (or both) incompatibility were included. The use of exchange transfusion decreased significantly in the immunoglobulin treated group (typical RR 0.35, 95% CI 0.25 to 0.49; typical RD -0.22, 95% CI -0.27 to

  15. 7(th) International Immunoglobulin Conference: Poster presentations.

    Science.gov (United States)

    Warnatz, K; Ballow, M; Stangel, M; Bril, V

    2014-12-01

    Immunoglobulin (Ig) therapy is the mainstay of treatment for primary antibody deficiency disorders and has proved to be efficacious in specific autoimmune and inflammatory diseases. Additionally, due to the role of Ig in complement activation, it is being used increasingly in solid organ transplantation. Furthermore, Ig is the primary or secondary treatment in some immune-mediated neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) or multifocal motor neuropathy (MMN). This session discusses trends of Ig use in Europe, proposed mechanisms of action, adverse effects and the potential role of Ig therapy in transplantation. Dr Šedivá reported that Ig therapy is available in all European countries, although dosing is not always optimal, due partly to reimbursement plans. Subcutaneous immunoglobulin (SCIg) has become increasingly accessible in recent years; however, the chosen route of administration still varies widely between countries. Dr Berger's presentation on optimization of Ig therapy in neuropathies, and Dr Rojavin's report on a pharmacometric model to determine the serum IgG levels achieved by different dosing regimens in primary antibody deficiency (PAD) patients, led to the challenging concept of using individualized dosing strategies. Dr Klehmet reported on the potential benefit of using antigen-specific T cell responses as a biomarker of IVIg responsiveness in CIDP patients, while Dr von Gunten provided an insight into the mechanisms of action of Ig preparations, suggesting that the immunoregulatory effects of IgG may be mediated by IgG antibodies against glycans. Dr Basta reported on the potential thrombogenic adverse effects associated with Ig therapy. Although these adverse events are rare, further studies are needed to clarify the relationship between Ig replacement and immunomodulatory therapy and these adverse reactions. In transplantation, Dr Carbone described that prophylactic IVIg treatment was found to decrease the

  16. Pattern of intravenous immunoglobulins (IVIG) use in a pediatric ...

    African Journals Online (AJOL)

    Pattern of intravenous immunoglobulins (IVIG) use in a pediatric intensive care facility in a resource limited setting. ... Journal Home > Vol 13, No 2 (2013) > ... Results: The clinical diagnoses included neurology (35%), neonatology (16%), ...

  17. Beneficial use of immunoglobulins in the treatment of Sydenham chorea

    NARCIS (Netherlands)

    T.D. van Immerzeel (Tabitha); R.M. van Gilst (Ruud); N.G. Hartwig (Nico)

    2010-01-01

    textabstractThis double case report indicates that treatment with intravenous immunoglobulins (IVIG) is effective in patients with Sydenham chorea (SC). SC is a rare but impressive clinical manifestation following streptococcal infection. This movement disorder characterised by chorea, emotional

  18. Human placental immunoglobulins show unique re-association ...

    African Journals Online (AJOL)

    Objective: To study re-association pattern of human placental eluate immunoglobulins with acid treated isologous and third party trophoblast derived placental microvesicles. Design: Laboratory based experimentation. Setting: Biological Sciences Department and Discipline for Reproductive Medicine University of ...

  19. Prevalence of Rhesus Negative Gene and Awareness of its ...

    African Journals Online (AJOL)

    The prevalence of the Rhesus negative gene was 7.5%. Only 5% were aware of the implications of Rhesus status. The prevalence is comparable with previous reports, the use of anti-D immunoglobulin is advised when appropriate. Key Words: Rhesus negative, genotype anti-D immunoglobulin. Jnl of Medical Investigation ...

  20. Cerebrospinal fluid aquaporin-4-immunoglobulin G disrupts blood brain barrier

    DEFF Research Database (Denmark)

    Asgari, Nasrin; Berg, Carsten Tue; Mørch, Marlene Thorsen

    2015-01-01

    associated with blood-borne horseradish peroxidase leakage indicating blood-brain barrier breakdown. The cerebrospinal fluid aquaporin-4-immunoglobulin G therefore distributes widely in brain to initiate astrocytopathy and blood-brain barrier breakdown....... was evaluated. A distinct distribution pattern of aquaporin-4-immunoglobulin G deposition was observed in the subarachnoid and subpial spaces where vessels penetrate the brain parenchyma, via a paravascular route with intraparenchymal perivascular deposition. Perivascular astrocyte-destructive lesions were...

  1. Purification, characterization and ELISA detection of mink immunoglobulins

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Aasted, Bent

    2008-01-01

    the estimated molecular weights of the immunoglobulin gamma, alpha and mu heavy chains were found to be 54 kDa, 69 kDa and 83 kDa respectively. The purities of purified IgG, IgM and IgA were estimated by immunoglobulin class specific ELISAs to be more than 90% for IgG and IgM, and more than 80% for IgA....

  2. Immunoglobulin class-switch recombination deficiencies.

    Science.gov (United States)

    Durandy, Anne; Kracker, Sven

    2012-07-30

    Immunoglobulin class-switch recombination deficiencies (Ig-CSR-Ds) are rare primary immunodeficiencies characterized by defective switched isotype (IgG/IgA/IgE) production. Depending on the molecular defect in question, the Ig-CSR-D may be combined with an impairment in somatic hypermutation (SHM). Some of the mechanisms underlying Ig-CSR and SHM have been described by studying natural mutants in humans. This approach has revealed that T cell-B cell interaction (resulting in CD40-mediated signaling), intrinsic B-cell mechanisms (activation-induced cytidine deaminase-induced DNA damage), and complex DNA repair machineries (including uracil-N-glycosylase and mismatch repair pathways) are all involved in class-switch recombination and SHM. However, several of the mechanisms required for full antibody maturation have yet to be defined. Elucidation of the molecular defects underlying the diverse set of Ig-CSR-Ds is essential for understanding Ig diversification and has prompted better definition of the clinical spectrum of diseases and the development of increasingly accurate diagnostic and therapeutic approaches.

  3. Immunoglobulin diversification in B cell malignancies: internal splicing of heavy chain variable region as a by-product of somatic hypermutation

    NARCIS (Netherlands)

    Bende, R. J.; Aarts, W. M.; Pals, S. T.; van Noesel, C. J. M.

    2002-01-01

    In this study we describe alternative splicing of somatically mutated immunoglobulin (Ig) variable heavy chain (V-H) genes in three distinct primary B cell non-Hodgkin's lymphomas (B-NHL). In two V4-34 expressing lymphomas, ie a post-germinal center type B cell chronic lymphocytic leukemia (B-CLL)

  4. A new high molecular weight immunoglobulin class from the carcharhine shark: implications for the properties of the primordial immunoglobulin.

    Science.gov (United States)

    Berstein, R M; Schluter, S F; Shen, S; Marchalonis, J J

    1996-04-16

    All immunoglobulins and T-cell receptors throughout phylogeny share regions of highly conserved amino acid sequence. To identify possible primitive immunoglobulins and immunoglobulin-like molecules, we utilized 3' RACE (rapid amplification of cDNA ends) and a highly conserved constant region consensus amino acid sequence to isolate a new immunoglobulin class from the sandbar shark Carcharhinus plumbeus. The immunoglobulin, termed IgW, in its secreted form consists of 782 amino acids and is expressed in both the thymus and the spleen. The molecule overall most closely resembles mu chains of the skate and human and a new putative antigen binding molecule isolated from the nurse shark (NAR). The full-length IgW chain has a variable region resembling human and shark heavy-chain (VH) sequences and a novel joining segment containing the WGXGT motif characteristic of H chains. However, unlike any other H-chain-type molecule, it contains six constant (C) domains. The first C domain contains the cysteine residue characteristic of C mu1 that would allow dimerization with a light (L) chain. The fourth and sixth domains also contain comparable cysteines that would enable dimerization with other H chains or homodimerization. Comparison of the sequences of IgW V and C domains shows homology greater than that found in comparisons among VH and C mu or VL, or CL thereby suggesting that IgW may retain features of the primordial immunoglobulin in evolution.

  5. Serum immunoglobulin G4 levels and Graves' disease phenotype.

    Science.gov (United States)

    Martin, Carmen Sorina; Sirbu, Anca Elena; Betivoiu, Minodora Andreea; Florea, Suzana; Barbu, Carmen Gabriela; Fica, Simona Vasilica

    2017-02-01

    We investigated, at diagnosis, the relationship between serum immunoglobulin G4 levels and the main characteristics of Graves' disease: hyperthyroidism severity, goiter size, presence of active Graves' ophthalmopathy, antithyroid antibodies status, and titer. This prospective study included 80 newly diagnosed Graves' disease patients. The main parameters measured at diagnosis: thyroid-stimulating hormone, free thyroxine, free triiodothyronine, total triiodothyronine, thyroglobulin, antithyroid peroxidase antibodies, anti-thyroglobulin antibodies, thyroid-stimulating hormone receptor antibodies, immunoglobulin G4. In Graves' disease patients, serum immunoglobulin G4 levels were higher than in general population (p = 0.028) and higher in men compared to women (p = 0.002). Only one female patient with intense hypoechoic goiter, high anti-thyroglobulin antibody, and antithyroid peroxidase antibody titers had an elevated serum immunoglobulin G4 level at diagnosis. Patients with immunoglobulin G4 levels above the 75th percentile (>237.52 mg/dl, N = 20) were younger at Graves' ophthalmopathy onset (p 286.28 mg/dl, N = 8) had lower total triiodothyronine values (p = 0.001) than patients with IgG below the 90th percentile. No significant correlations were found between smoking status (p = 0.58), goiter size (p = 0.50), the presence of ophthalmopathy (p = 0.42) or thyroid-stimulating hormone receptor antibody titers (p = 0.45) and the mean value of immunoglobulin G4 levels at diagnosis. Our data suggest that Graves' disease patients with elevated immunoglobulin G4 levels at diagnosis have a phenotype characterized by higher anti-thyroglobulin antibody and antithyroid peroxidase antibody titers, less severe T3 hyperthyroidism, younger age at ophthalmopathy onset and require a shorter duration of the first methimazole treatment cycle.

  6. The Unusual Genetics and Biochemistry of Bovine Immunoglobulins.

    Science.gov (United States)

    Stanfield, Robyn L; Haakenson, Jeremy; Deiss, Thaddeus C; Criscitiello, Michael F; Wilson, Ian A; Smider, Vaughn V

    2018-01-01

    Antibodies are the key circulating molecules that have evolved to fight infection by the adaptive immune system of vertebrates. Typical antibodies of most species contain six complementarity-determining regions (CDRs), where the third CDR of the heavy chain (CDR H3) has the greatest diversity and often makes the most significant contact with antigen. Generally, the process of V(D)J recombination produces a vast repertoire of antibodies; multiple V, D, and J gene segments recombine with additional junctional diversity at the V-D and D-J joints, and additional combinatorial possibilities occur through heavy- and light-chain pairing. Despite these processes, the overall structure of the resulting antibody is largely conserved, and binding to antigen occurs predominantly through the CDR loops of the immunoglobulin V domains. Bovines have deviated from this general paradigm by having few VH regions and thus little germline combinatorial diversity, but their antibodies contain long CDR H3 regions, with substantial diversity generated through somatic hypermutation. A subset of the repertoire comprises antibodies with ultralong CDR H3s, which can reach over 70 amino acids in length. Structurally, these unusual antibodies form a β-ribbon "stalk" and disulfide-bonded "knob" that protrude far from the antibody surface. These long CDR H3s allow cows to mount a particularly robust immune response when immunized with viral antigens, particularly to broadly neutralizing epitopes on a stabilized HIV gp140 trimer, which has been a challenge for other species. The unusual genetics and structural biology of cows provide for a unique paradigm for creation of immune diversity and could enable generation of antibodies against especially challenging targets and epitopes. © 2018 Elsevier Inc. All rights reserved.

  7. Large-scale chromatin remodeling at the immunoglobulin heavy chain locus: a paradigm for multigene regulation.

    Science.gov (United States)

    Bolland, Daniel J; Wood, Andrew L; Corcoran, Anne E

    2009-01-01

    V(D)J recombination in lymphocytes is the cutting and pasting together of antigen receptor genes in cis to generate the enormous variety of coding sequences required to produce diverse antigen receptor proteins. It is the key role of the adaptive immune response, which must potentially combat millions of different foreign antigens. Most antigen receptor loci have evolved to be extremely large and contain multiple individual V, D and J genes. The immunoglobulin heavy chain (Igh) and immunoglobulin kappa light chain (Igk) loci are the largest multigene loci in the mammalian genome and V(D)J recombination is one of the most complicated genetic processes in the nucleus. The challenge for the appropriate lymphocyte is one of macro-management-to make all of the antigen receptor genes in a particular locus available for recombination at the appropriate developmental time-point. Conversely, these large loci must be kept closed in lymphocytes in which they do not normally recombine, to guard against genomic instability generated by the DNA double strand breaks inherent to the V(D)J recombination process. To manage all of these demanding criteria, V(D)J recombination is regulated at numerous levels. It is restricted to lymphocytes since the Rag genes which control the DNA double-strand break step of recombination are only expressed in these cells. Within the lymphocyte lineage, immunoglobulin recombination is restricted to B-lymphocytes and TCR recombination to T-lymphocytes by regulation of locus accessibility, which occurs at multiple levels. Accessibility of recombination signal sequences (RSSs) flanking individual V, D and J genes at the nucleosomal level is the key micro-management mechanism, which is discussed in greater detail in other chapters. This chapter will explore how the antigen receptor loci are regulated as a whole, focussing on the Igh locus as a paradigm for the mechanisms involved. Numerous recent studies have begun to unravel the complex and

  8. Bacteriostatic enterochelin-specific immunoglobulin from normal human serum

    Energy Technology Data Exchange (ETDEWEB)

    Moore, D.G.; Yancey, R.J.; Lankford, C.E.; Earhart, C.F.

    1980-02-01

    Heat-inactivated normal human serum produces iron-reversible bacteriostasis of a number of microorganisms. This inhibitory effect was abolished by adsorption of serum with ultraviolet-killed cells of species that produce the siderophore enterochelin. Bacteriostasis also was alleviated by asorption of serum with 2,3-dihydroxy-N-benzoyl-L-serine, a degradation product of enterochelin, bound to the insoluble matrix AH-Sepharose 4B. Our results indicate that enterochelin-specific immunoglobulins exist in normal human serum. These immunoglobulins may act synergistically with transferrin to effect bacteriostasis of enterochelin-producing pathogens.

  9. Serum immunoglobulin E and immunoglobulin G reactivity to Agaricus bisporus proteins in mushroom cultivation workers.

    Science.gov (United States)

    Khakzad, Z; Hedayati, M T; Mahdian, S; Mayahi, S

    2015-06-01

    Although molds are regarded as the main fungal allergen sources, evidence indicates that spores of Basidiomycota including Agaricus bisporus ( A. bisporus ) can be also found at high concentrations in the environment and may cause as many respiratory allergies as molds. The aim of the present study was to evaluate specific immunoglobulin E (IgE) and immunoglobulin G (IgG) antibodies against A. bisporus via immunoblotting technique in individuals working at mushroom cultivation centers. In this study, 72 workers involved in the cultivation and harvest of button mushrooms were enrolled. For the analysis of serum IgE and IgG, A. bisporus grown in Sabouraud dextrose broth was harvested and ruptured by liquid nitrogen and glass beads. The obtained sample was centrifuged and the supernatant was collected as "crude extract" (CE). CE was separated via Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE). The separated proteins were transferred to a nitrocellulose filter and the bands responsive to IgE and IgG were identified by anti-human conjugated antibodies. All participants were screened in terms of total IgE level. Among 72 workers, 18 (25%) had a total IgE level higher than 188 IU/mL. In SDS-PAGE, the CE of A. bisporus showed 23 different protein bands with a molecular weight range of 13-80 kDa. The sera of 23.6% and 55.5% of participants showed positive response, with specific IgE and IgG antibodies against A. bisporus in the blot, respectively. The bands with molecular weights of 62 and 68 kDa were the most reactive protein components of A. bisporus to specific IgE antibodies. Moreover, bands with molecular weights of 57 and 62 kDa showed the highest reactivity to IgG, respectively. Also, 62 and 68 kDa components were the most reactive bands with both specific IgG and IgE antibodies. The obtained findings revealed that A. bisporus has different allergens and antigens, which contribute to its potential as an aeroallergen in hypersensitivity

  10. 21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fab fragment specific... Test Systems § 866.5520 Immunoglobulin G (Fab fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fab fragment specific) immunological test system is a device that consists...

  11. 21 CFR 866.5540 - Immunoglobulin G (Fd fragment specific) immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fd fragment specific... Test Systems § 866.5540 Immunoglobulin G (Fd fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fd fragment specific) immunological test system is a device that consists of...

  12. 21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fc fragment specific... Test Systems § 866.5530 Immunoglobulin G (Fc fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fc fragment specific) immunological test system is a device that consists of...

  13. Acute phase proteins and immunoglobulin classes in newly ...

    African Journals Online (AJOL)

    Background: No single organic cause has been found for schizophrenia and its management has been difficult. More so, there are few data on the immune parameters of Nigerian schizophrenic patients on drug treatment and those that are not on treatment. Methodology: This study determines the levels of immunoglobulin

  14. Pattern of intravenous immunoglobulins (IVIG) use in a pediatric ...

    African Journals Online (AJOL)

    EB

    Abstract. Background: Intravenous Immunoglobulin (IVIG) preparations are scarce biological products used for replacement or immunomodulatory effects. Guidelines have been issued by regulatory health authorities to ensure provision of the products for patients who are in severe need. Objectives: The study aimed at ...

  15. Rhesus anti-D immunoglobulin in chronic autoimmune neuropathy

    NARCIS (Netherlands)

    de Jager, AEJ; van der Hoeven, JH

    Objective - To investigate the effect of Rhesus anti-D immunoglobulin (anti-D) in patients with an autoimmune demyelinating neuropathy. Material and methods - Three patients with an autoimmune mediated neuropathy received 1000 IU anti-D weekly for 2 months. Results - Two patients worsened gradually

  16. Sensitive chain specific radioimmunoassay for human immunoglobulins using monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Sikora, K; Alderson, T St.J.; Ellis, J [Ludwig Institute for Cancer Research, Cambridge (UK)

    1983-02-25

    A sensitive radioimmunoassay is described for human immunoglobulins. This solid-phase assay uses commercially available monoclonal antibodies and is specific for different Ig chain types. Levels of less than 20 ng/ml Ig are detectable. The assay is suitable for the analysis of human hybridoma supernatants.

  17. Immunoglobulin therapy in hematologic neoplasms and after hematopoietic cell transplantation.

    Science.gov (United States)

    Ueda, Masumi; Berger, Melvin; Gale, Robert Peter; Lazarus, Hillard M

    2018-03-01

    Immunoglobulins are used to prevent or reduce infection risk in primary immune deficiencies and in settings which exploit its anti-inflammatory and immune-modulatory effects. Rigorous proof of immunoglobulin efficacy in persons with lympho-proliferative neoplasms, plasma cell myeloma, and persons receiving hematopoietic cell transplants is lacking despite many clinical trials. Further, there are few consensus guidelines or algorithms for use in these conditions. Rapid development of new therapies targeting B-cell signaling and survival pathways and increased use of chimeric antigen receptor T-cell (CAR-T) therapy will likely result in more acquired deficiencies of humoral immunity and infections in persons with cancer. We review immunoglobulin formulations and discuss efficacy and potential adverse effects in the context of preventing infections and in graft-versus-host disease. We suggest an algorithm for evaluating acquired deficiencies of humoral immunity in persons with hematologic neoplasms and recommend appropriate use of immunoglobulin therapy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Alpha chain determinants on the membrane of immunoglobulin synthesizing cells

    NARCIS (Netherlands)

    Hijmans, W.; Schuit, H.R.E.; Radl, J.; Vossen, J.M.J.J.

    1974-01-01

    In a study of surface immunoglobulins (Ig) on lymphocytes from patients with paraproteinemia (1), we observed that a variable number of plasma cells not only contained intracellular Ig, but also had Ig on their surface, as shown in the vital technique of immunofluorescence. Moreover, in the bone

  19. Bacteremia and immunoglobulin classes in Nigerian women with ...

    African Journals Online (AJOL)

    Apart from antiphospholipid- and thyroid- autoantibodies which were reported as underlying causes of recurrent pregnancy loss, specific IgG to patermal MHC and Rh was proposed. This raises the possibility of other classes of immunoglobulin in recurrent abortion. Twenty-four pregnant women with recurrent abortion ...

  20. serum immunoglobulin levels in white, asiatic and bantu blood donors

    African Journals Online (AJOL)

    all assays were calculated as a percentage of the mean of. TABLE I. RESULTS OF IMMUNOGLOBULIN ASSAYS OF tOO WHITE, tOO ASIATIC AND 100 BANTU DONORS, EXPRESSED AS A. PERCENTAGE OF A CONTROL SERUM. Parameter. Range. Mean. Variance. Standard deviation. CoefI. of variation.

  1. Haemolytic anaemia as a complication to intravenous immunoglobulin infusion

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Harbo, Thomas; Christiansen, Ingelise

    performed before and two weeks after infusion of IVIg. Following treatment blood haemoglobin declined from 8.6±0.8 to 8.1±1.3mmol/l, p... naive patients are susceptible to develop haemolysis. Haemolytic anaemia is a severe side effect that seems to be more frequent after immunoglobulin infusions than previously recognized....

  2. Solvent-Detergent Treatment of IgM-Enriched Immunoglobulin

    Directory of Open Access Journals (Sweden)

    Mojgan Pourmokhtar

    2003-08-01

    Full Text Available Viral safety of human plasma products plays a key role in their safe uses. Solvent- detergent (SD virus-inactivation method has gained widespread popularity in the manufacture of biological products. This treatment which inactivates lipid-enveloped viruses effectively consists of incubation of a plasma protein solution in the presence of a non-volatile organic solvent and a detergent. In this study, IgM-enriched immunoglobulin was incubated at 24 °C for 6 h under slow stirring in the presence of tri(n-butyl phosphate (0.3% w/w as solvent and tween 80 (1% w/w as detergent. After completion of the inactivation process and removal of the solvent-detergent, the ability of SD-treatment to remove Infectious Bovine Rhinotracheitis (IBR virus (a lipid-enveloped virus and Foot-and-Mouth Disease virus (a non-enveloped virus were evaluated by "virus spiking studies" using a scaled down process. Reduction factor of 4 log was obtained for the SD-treatment of IgM-enriched immunoglobulin spiked with IBR virus. No virus inactivation was observed in the SD-treated IgM-enriched immunoglobulin, spiked with Foot-and-Mouth Disease virus. It was concluded that treatment of IgM-enriched immunoglobulin with TNBP-TWEEN 80 may be considered as an efficient lipid-enveloped virus inactivation step in the manufacture of this product.

  3. Mechanism of immunoglobulin G4 Fab-arm exchange

    NARCIS (Netherlands)

    Rispens, Theo; Ooijevaar-de Heer, Pleuni; Bende, Onno; Aalberse, Rob C.

    2011-01-01

    Immunoglobulin G (IgG) antibodies are symmetrical molecules that may be regarded as covalent dimers of 2 half-molecules, each consisting of a light chain and a heavy chain. Human IgG4 is an unusually dynamic antibody, with half-molecule exchange ("Fab-arm exchange") resulting in asymmetrical,

  4. Effect of continuous milking on immunoglobulin concentrations in bovine colostrum

    NARCIS (Netherlands)

    Verweij, J.J.; Koets, A.P.; Eisenberg, S.W.F.

    2014-01-01

    Continuous milking is defined as a dairy cattle management system without a planned dry period for cows in late gestation. Continuous milking has been described to reduce health problems common in periparturient cattle, but may affect colostrum immunoglobulin (Ig) concentration and subsequently calf

  5. Pathogenic Leptospira species express surface-exposed proteins belonging to the bacterial immunoglobulin superfamily

    Science.gov (United States)

    Matsunaga, James; Barocchi, Michele A.; Croda, Julio; Young, Tracy A.; Sanchez, Yolanda; Siqueira, Isadora; Bolin, Carole A.; Reis, Mitermayer G.; Riley, Lee W.; Haake, David A.; Ko, Albert I.

    2005-01-01

    Summary Proteins with bacterial immunoglobulin-like (Big) domains, such as the Yersinia pseudotuberculosis invasin and Escherichia coli intimin, are surface-expressed proteins that mediate host mammalian cell invasion or attachment. Here, we report the identification and characterization of a new family of Big domain proteins, referred to as Lig (leptospiral Ig-like) proteins, in pathogenic Leptospira. Screening of L. interrogans and L. kirschneri expression libraries with sera from leptospirosis patients identified 13 lambda phage clones that encode tandem repeats of the 90 amino acid Big domain. Two lig genes, designated ligA and ligB, and one pseudo-gene, ligC, were identified. The ligA and ligB genes encode amino-terminal lipoprotein signal peptides followed by 10 or 11 Big domain repeats and, in the case of ligB, a unique carboxy-terminal non-repeat domain. The organization of ligC is similar to that of ligB but contains mutations that disrupt the reading frame. The lig sequences are present in pathogenic but not saprophytic Leptospira species. LigA and LigB are expressed by a variety of virulent leptospiral strains. Loss of Lig protein and RNA transcript expression is correlated with the observed loss of virulence during culture attenuation of pathogenic strains. High-pressure freeze substitution followed by immunocytochemical electron microscopy confirmed that the Lig proteins were localized to the bacterial surface. Immunoblot studies with patient sera found that the Lig proteins are a major antigen recognized during the acute host infection. These observations demonstrate that the Lig proteins are a newly identified surface protein of pathogenic Leptospira, which by analogy to other bacterial immunoglobulin superfamily virulence factors, may play a role in host cell attachment and invasion during leptospiral pathogenesis. PMID:12890019

  6. Analysis of immunoglobulin transcripts in the ostrich Struthio camelus, a primitive avian species.

    Directory of Open Access Journals (Sweden)

    Tian Huang

    Full Text Available Previous studies on the immunoglobulin (Ig genes in avian species are limited (mainly to galliformes and anseriformes but have revealed several interesting features, including the absence of the IgD and Igκ encoding genes, inversion of the IgA encoding gene and the use of gene conversion as the primary mechanism to generate an antibody repertoire. To better understand the Ig genes and their evolutionary development in birds, we analyzed the Ig genes in the ostrich (Struthio camelus, which is one of the most primitive birds. Similar to the chicken and duck, the ostrich expressed only three IgH chain isotypes (IgM, IgA and IgY and λ light chains. The IgM and IgY constant domains are similar to their counterparts described in other vertebrates. Although conventional IgM, IgA and IgY cDNAs were identified in the ostrich, we also detected a transcript encoding a short membrane-bound form of IgA (lacking the last two C(H exons that was undetectable at the protein level. No IgD or κ encoding genes were identified. The presence of a single leader peptide in the expressed heavy chain and light chain V regions indicates that gene conversion also plays a major role in the generation of antibody diversity in the ostrich. Because the ostrich is one of the most primitive living aves, this study suggests that the distinct features of the bird Ig genes appeared very early during the divergence of the avian species and are thus shared by most, if not all, avian species.

  7. Effects of spaceflight on the immunoglobulin repertoire of unimmunized C57BL/6 mice

    Science.gov (United States)

    Ward, Claire; Rettig, Trisha A.; Hlavacek, Savannah; Bye, Bailey A.; Pecaut, Michael J.; Chapes, Stephen K.

    2018-02-01

    Spaceflight has been shown to suppress the adaptive immune response, altering the distribution and function of lymphocyte populations. B lymphocytes express highly specific and highly diversified receptors, known as immunoglobulins (Ig), that directly bind and neutralize pathogens. Ig diversity is achieved through the enzymatic splicing of gene segments within the genomic DNA of each B cell in a host. The collection of Ig specificities within a host, or Ig repertoire, has been increasingly characterized in both basic research and clinical settings using high-throughput sequencing technology (HTS). We utilized HTS to test the hypothesis that spaceflight affects the B-cell repertoire. To test this hypothesis, we characterized the impact of spaceflight on the unimmunized Ig repertoire of C57BL/6 mice that were flown aboard the International Space Station (ISS) during the Rodent Research One validation flight in comparison to ground controls. Individual gene segment usage was similar between ground control and flight animals, however, gene segment combinations and the junctions in which gene segments combine was varied among animals within and between treatment groups. We also found that spontaneous somatic mutations in the IgH and Igκ gene loci were not increased. These data suggest that space flight did not affect the B cell repertoire of mice flown and housed on the ISS over a short period of time.

  8. Killer immunoglobulin-like receptor (KIR and HLA genotypes affect the outcome of allogeneic kidney transplantation.

    Directory of Open Access Journals (Sweden)

    Izabela Nowak

    Full Text Available BACKGROUND: Recipient NK cells may detect the lack of recipient's (i.e., self HLA antigens on donor renal tissue by means of their killer cell immunoglobulin-like receptors (KIRs. KIR genes are differently distributed in individuals, possibly contributing to differences in response to allogeneic graft. METHODOLOGY/PRINCIPAL FINDINGS: We compared frequencies of 10 KIR genes by PCR-SSP in 93 kidney graft recipients rejecting allogeneic renal transplants with those in 190 recipients accepting grafts and 690 healthy control individuals. HLA matching results were drawn from medical records. We observed associations of both a full-length KIR2DS4 gene and its variant with 22-bp deletion with kidney graft rejection. This effect was modulated by the HLA-B,-DR matching, particularly in recipients who did not have glomerulonephritis but had both forms of KIR2DS4 gene. In contrast, in recipients with glomerulonephritis, HLA compatibility seemed to be much less important for graft rejection than the presence of KIR2DS4 gene. Simultaneous presence of both KIR2DS4 variants strongly increased the probability of rejection. Interestingly, KIR2DS5 seemed to protect the graft in the presence of KIR2DS4fl but in the absence of KIR2DS4del. CONCLUSIONS/SIGNIFICANCE: Our results suggest a protective role of KIR2DS5 in graft rejection and an association of KIR2DS4 with kidney rejection, particularly in recipients with glomerulonephritis.

  9. Immunoglobulin concentration in blood serum of postcolostral calves: Ratio between immunoglobulin level and appearance of enzootic pneumonia

    Directory of Open Access Journals (Sweden)

    Jonić Branko

    2007-01-01

    Full Text Available The timely supply of newborn calves with optimal quantities of colostrum has a key role in the process of immune protection in the early phase of their lives. Passively acquired antibodies can protect the digestive organs from infection caused by E.coli bacteria, and it seems also from the appearance of diseases of the respiratory tract. These examinations were performed on a cattle farm where bronchopneumonia was one of the most significant health problems, and a group of 39 calves were selected for the investigations. The calves were fed with their mothers’ colostrum after birth, and then with collective milk. Immunoglobulin concentration was determined in blood samples taken during the postcolostral period, with the method using zinc-sulphate. At the age of 40 days, the calves were administered a polyvalent inactivated vaccine, and revaccinated 20 days after that (Vibak, Veterinary Department Subotica. In 74.34% calves, the immunoglobulin G concentration ranged from 26 to 40 g/l. In 25.66% calves, the immunoglobulin concentration was lower, from 8 to 25 g/l. The calves found to have a lower concentration of immunoglobulin in blood contracted bronchopneumonia more frequently, and the outcome of the disease in some cases was mortality, even.

  10. Comparison of techniques of detecting immunoglobulin-binding protein reactivity to immunoglobulin produced by different avian and mammalian species.

    Science.gov (United States)

    Justiz-Vaillant, A A; Akpaka, P E; McFarlane-Anderson, N; Smikle, M F

    2013-01-01

    The rationale of this study was to use several immunological assays to investigate the reactivity of immunoglobulin binding protein (IBP) to immunoglobulins from various avian and mammalian species. The IBP studied were Staphylococcal protein A (SpA), Streptococcal protein G (SpG), Peptostreptococcal protein L (SpL) and recombinant protein LA (SpLA). The various immunological techniques used were double immunodiffusion (Ouchterlony technique) that tested positive high protein reactivities, direct and competitive enzyme-linked immunosorbent assays (ELISAs) that tested moderate and low positive protein binding capacities, respectively. In addition to sandwich ELISAs, immunoblot analyses and Ig-purification by SpA-affinity chromatography, which were sensitive tests and helpful in the screening and confirmatory tests were also used. The Ouchterlony technique showed that compared to the other proteins, SpLA had the highest range of reactivity with animal sera and purified immunoglobulins while SpL was least reactive. With the direct ELISA, SpL reacted with the raccoon sera, rabbit IgG and with IgY from bantam hens and pigeons. While with the direct ELISA, SpA reacted with sera from skunk, coyote, raccoon, mule, donkey and human. The sandwich ELISA revealed high reactivity of both SpG and SpLA with mammalian sera titres ranging from 1:32 (raccoon serum) to 1:1024 (mule and donkey sera). These results suggest that IBP can be used for the detection of immunoglobulin using various immunological assays and this is important for the diagnosis of infectious diseases in animal and bird populations studied and in the purification of immunoglobulins.

  11. High levels of immunoglobulin E and a continuous increase in immunoglobulin G and immunoglobulin M by age in children with newly diagnosed type 1 diabetes

    DEFF Research Database (Denmark)

    Svensson, Jannet; Eising, Stefanie; Mortensen, Henrik Bindesbøl

    2012-01-01

    The incidence of type 1 diabetes (T1D) is increasing, either because of environmental factors accelerating onset of the disease or because of inducement of autoimmune diabetes in children who previously were at lower risk. High levels of immunoglobulin (Ig), specifically, IgM and IgA, and a low...... level of IgG were reported in adult patients; however no studies have analyzed the increasing incidence in relation to Ig levels. Our aim was to describe Ig in children newly diagnosed with diabetes and in their healthy siblings. Children with T1D expressed significantly lower IgG (p

  12. Autoantibodies and immunoglobulins in alcoholic steatosis and cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Tage-Jensen, Ulrik Viggo

    1983-01-01

    increased (p less than 0.005) concentrations of immunoglobulins G, A, and M when compared to patients with steatosis. These results indicate that the degree of liver damage has more effect than chronic alcoholism on the humoral immune system. Whether this influence is direct or indirect remains......Antinuclear antibodies were significantly more prevalent (p less than 0.01) in 143 patients with alcoholic cirrhosis than in 64 patients with alcoholic steatosis and in 94 controls. Smooth muscle antibodies were significantly more prevalent (p less than 0.05) in patients with alcoholic steatosis...... and cirrhosis than in controls. The prevalence of antimitochondrial antibodies and IgG liver membrane antibodies did not differ significantly between the three groups. Immunoglobulin G, A, and M concentrations were only occasionally increased in patients with steatosis. Patients with cirrhosis had significantly...

  13. A role for PCNA ubiquitination in immunoglobulin hypermutation.

    Directory of Open Access Journals (Sweden)

    Hiroshi Arakawa

    2006-11-01

    Full Text Available Proliferating cell nuclear antigen (PCNA is a DNA polymerase cofactor and regulator of replication-linked functions. Upon DNA damage, yeast and vertebrate PCNA is modified at the conserved lysine K164 by ubiquitin, which mediates error-prone replication across lesions via translesion polymerases. We investigated the role of PCNA ubiquitination in variants of the DT40 B cell line that are mutant in K164 of PCNA or in Rad18, which is involved in PCNA ubiquitination. Remarkably, the PCNA(K164R mutation not only renders cells sensitive to DNA-damaging agents, but also strongly reduces activation induced deaminase-dependent single-nucleotide substitutions in the immunoglobulin light-chain locus. This is the first evidence, to our knowledge, that vertebrates exploit the PCNA-ubiquitin pathway for immunoglobulin hypermutation, most likely through the recruitment of error-prone DNA polymerases.

  14. A database of immunoglobulins with integrated tools: DIGIT.

    KAUST Repository

    Chailyan, Anna; Tramontano, Anna; Marcatili, Paolo

    2011-01-01

    The DIGIT (Database of ImmunoGlobulins with Integrated Tools) database (http://biocomputing.it/digit) is an integrated resource storing sequences of annotated immunoglobulin variable domains and enriched with tools for searching and analyzing them. The annotations in the database include information on the type of antigen, the respective germline sequences and on pairing information between light and heavy chains. Other annotations, such as the identification of the complementarity determining regions, assignment of their structural class and identification of mutations with respect to the germline, are computed on the fly and can also be obtained for user-submitted sequences. The system allows customized BLAST searches and automatic building of 3D models of the domains to be performed.

  15. A database of immunoglobulins with integrated tools: DIGIT.

    KAUST Repository

    Chailyan, Anna

    2011-11-10

    The DIGIT (Database of ImmunoGlobulins with Integrated Tools) database (http://biocomputing.it/digit) is an integrated resource storing sequences of annotated immunoglobulin variable domains and enriched with tools for searching and analyzing them. The annotations in the database include information on the type of antigen, the respective germline sequences and on pairing information between light and heavy chains. Other annotations, such as the identification of the complementarity determining regions, assignment of their structural class and identification of mutations with respect to the germline, are computed on the fly and can also be obtained for user-submitted sequences. The system allows customized BLAST searches and automatic building of 3D models of the domains to be performed.

  16. CD147 Immunoglobulin Superfamily Receptor Function and Role in Pathology

    OpenAIRE

    Iacono, Kathryn T.; Brown, Amy L.; Greene, Mark I.; Saouaf, Sandra J.

    2007-01-01

    The immunoglobulin superfamily member CD147 plays an important role in fetal, neuronal, lymphocyte and extracellular matrix development. Here we review the current understanding of CD147 expression and protein interactions with regard to CD147 function and its role in pathologic conditions including heart disease, Alzheimer’s disease, stroke and cancer. A model linking hypoxic conditions found within the tumor microenvironment to up-regulation of CD147 expression and tumor progression is intr...

  17. Serologic activity of G immunoglobulin of irradiated rabbits

    International Nuclear Information System (INIS)

    Ivanov, A.A.; Nevinnaya, A.P.; Mozhajskij, A.M.; Snisar', N.A.

    1977-01-01

    Serologic immunochemical properties of immunoglobulins G (IgG) isolated from blood serum of normal rabbits and those given lethal and midlethal doses of radiation have been comparatively studied. A marked increase in the IgG level was detected in the recovery period of radiation sickness. The number of complement-binding antitissue antibodies in IgG grew in that period, and the anticomplementary activity and the catabolism rate of IgG increased in normal organism

  18. Immunoglobulin G4-related disease: autoimmune pancreatitis and extrapancreatic manifestations

    Directory of Open Access Journals (Sweden)

    Daniel Alvarenga Fernandes

    2016-04-01

    Full Text Available Abstract We present a case of immunoglobulin G4 (IgG4-related disease with pancreatic and extrapancreatic involvement, including the biliary and renal systems. Given the importance of imaging methods for the diagnosis of IgG4-related disease and its differentiation from pancreatic adenocarcinoma, we emphasize important abdominal computed tomography and magnetic resonance imaging findings related to this recently recognized systemic autoimmune disease.

  19. FCGR2A Promoter Methylation and Risks for Intravenous Immunoglobulin Treatment Responses in Kawasaki Disease

    Directory of Open Access Journals (Sweden)

    Ho-Chang Kuo

    2015-01-01

    Full Text Available Kawasaki disease (KD is characterized by pediatric systemic vasculitis of an unknown cause. The low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A gene was reported to be involved in the susceptibility of KD. DNA methylation is one of the epigenetic mechanisms that control gene expression; thus, we hypothesized that methylation status of CpG islands in FCGR2A promoter associates with the susceptibility and therapeutic outcomes of Kawasaki disease. In this study, 36 KD patients and 24 healthy subjects from out-patient clinic were recruited. Eleven potential methylation sites within the targeted promoter region of FCGR2A were selected for investigation. We marked the eleven methylation sites from A to K. Our results indicated that methylation at the CpG sites G, H, and J associated with the risk of KD. CpG sites B, C, E, F, H, J, and K were found to associate with the outcomes of IVIG treatment. In addition, CpG sites G, J, and K were predicted as transcription factors binding sites for NF-kB, Myc-Max, and SP2, respectively. Our study reported a significant association among the promoter methylation of FCGR2A, susceptibility of KD, and the therapeutic outcomes of IVIG treatment. The methylation levels of CpG sites of FCGR2A gene promoter should be an important marker for optimizing IVIG therapy.

  20. Generating and repairing genetically programmed DNA breaks during immunoglobulin class switch recombination

    Science.gov (United States)

    Nicolas, Laura; Cols, Montserrat; Choi, Jee Eun; Chaudhuri, Jayanta; Vuong, Bao

    2018-01-01

    Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR. Within the Ig locus, DNA repair pathways are diverted from their canonical role in maintaining genomic integrity to permit AID-directed mutation and deletion of gene coding segments. Recently identified proteins, genes, and regulatory networks have provided new insights into the temporally and spatially coordinated molecular interactions that control the formation and repair of DSBs within the Ig locus. Unravelling the genetic program that allows B cells to selectively alter the Ig coding regions while protecting non-Ig genes from DNA damage advances our understanding of the molecular processes that maintain genomic integrity as well as humoral immunity. PMID:29744038

  1. Central importance of immunoglobulin A in host defense against Giardia spp.

    Science.gov (United States)

    Langford, T Dianne; Housley, Michael P; Boes, Marianne; Chen, Jianzhu; Kagnoff, Martin F; Gillin, Frances D; Eckmann, Lars

    2002-01-01

    The protozoan pathogen Giardia is an important cause of parasitic diarrheal disease worldwide. It colonizes the lumen of the small intestine, suggesting that effective host defenses must act luminally. Immunoglobulin A (IgA) antibodies are presumed to be important for controlling Giardia infection, but direct evidence for this function is lacking. B-cell-independent effector mechanisms also exist and may be equally important for antigiardial host defense. To determine the importance of the immunoglobulin isotypes that are transported into the intestinal lumen, IgA and IgM, for antigiardial host defense, we infected gene-targeted mice lacking IgA-expressing B-cells, IgM-secreting B-cells, or all B-cells as controls with Giardia muris or Giardia lamblia GS/M-83-H7. We found that IgA-deficient mice could not eradicate either G. muris or G. lamblia infection, demonstrating that IgA is required for their clearance. Furthermore, although neither B-cell-deficient nor IgA-deficient mice could clear G. muris infections, IgA-deficient mice controlled infection significantly better than B-cell-deficient mice, suggesting the existence of B-cell-dependent but IgA-independent antigiardial defenses. In contrast, mice deficient for secreted IgM antibodies cleared G. muris infection normally, indicating that they have no unique functions in antigiardial host defense. These data, together with the finding that B-cell-deficient mice have some, albeit limited, residual capacity to control G. muris infection, show that IgA-dependent host defenses are central for eradicating Giardia spp. Moreover, B-cell-dependent but IgA-independent and B-cell-independent antigiardial host defenses exist but are less important for controlling infection.

  2. The association between immunoglobulin concentrations and prediabetes prevalence in a large Chinese cohort.

    Science.gov (United States)

    Wang, Honglei; Song, Yanqi; Sun, Shaomei; Gao, Li; Liu, Li; Meng, Ge; Wu, Hongmei; Xia, Yang; Bao, Xue; Gu, Yeqing; Shi, Hongbin; Su, Qian; Fang, Liyun; Yang, Huijun; Wang, Xing; Zhou, Ming; Jia, Qiyu; Song, Kun; Zhang, Qing; Niu, Kaijun

    2017-08-01

    Prediabetes has received public attention owing to the increasing prevalence worldwide. Mounting evidence has indicated that inflammation directly contributed to the etiology of glucose metabolism disorders. Although immunoglobulins play a crucial role in immune responses, little research has been done on the link between immunoglobulins and prediabetes in adults. Hence, the aim of the present study was to explore the associations between immunoglobulins levels and prevalence of prediabetes in a general adult population. A cross-sectional study was conducted among 8856 adults (mean±standard deviation age: 48.4±10.7years) in Tianjin, China. The serum immunoglobulins concentrations were measured by the immunonephelometric technique. Prediabetes was diagnosed using the following parameters in accordance with the American Diabetes Association: fasting plasma glucose, postprandial glucose and glycosylated hemoglobin. The associations between concentrations of immunoglobulins and the prevalence of prediabetes were assessed using multiple logistic regression models. Overall, the prevalence of prediabetes was 37.4% (3311/8856). After controlling for confounders, compared with the lowest quintile, the odds ratios (95% confidence interval) of prediabetes for the highest quintile of immunoglobulins (immunoglobulin G, immunoglobulin E, immunoglobulin M and immunoglobulin A) were as follows: 1.06 (0.91-1.23), 1.31 (1.13-1.52), 0.86 (0.74-1.01), and 1.19 (1.03-1.38) (P for trend were 0.35, prediabetes prevalence. There was also a trending association between immunoglobulin M concentrations and prediabetes prevalence. Further studies are necessary to clarify if there is a causal association of immunoglobulins in prediabetes or if they reflect early immunologic disturbances in these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Improved purification of immunoglobulin G from plasma by mixed-mode chromatography.

    Science.gov (United States)

    Chai, Dong-Sheng; Sun, Yan; Wang, Xiao-Ning; Shi, Qing-Hong

    2014-12-01

    Efficient loading of immunoglobulin G in mixed-mode chromatography is often a serious bottleneck in the chromatographic purification of immunoglobulin G. In this work, a mixed-mode ligand, 4-(1H-imidazol-1-yl) aniline, was coupled to Sepharose Fast Flow to fabricate AN SepFF adsorbents with ligand densities of 15-64 mmol/L, and the chromatographic performances of these adsorbents were thoroughly investigated to identify a feasible approach to improve immunoglobulin G purification. The results indicate that a critical ligand density exists for immunoglobulin G on the AN SepFF adsorbents. Above the critical ligand density, the adsorbents showed superior selectivity to immunoglobulin G at high salt concentrations, and also exhibited much higher dynamic binding capacities. For immunoglobulin G purification, both the yield and binding capacity increased with adsorbent ligand density along with a decrease in purity. It is difficult to improve the binding capacity, purity, and yield of immunoglobulin G simultaneously in AN SepFF chromatography. By using tandem AN SepFF chromatography, a threefold increase in binding capacity as well as high purity and yield of immunoglobulin G were achieved. Therefore, the tandem chromatography demonstrates that AN SepFF adsorbent is a practical and feasible alternative to MEP HyperCel adsorbents for immunoglobulin G purification. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Production of non-stimulatory immunoglobulins that inhibit TSH binding in Graves' disease after radioiodine administration

    International Nuclear Information System (INIS)

    Bech, K.; Bliddal, H.; Siersbaek-Nielsen, K.; Friis, T.

    1982-01-01

    The effect of single dose of 131 I upon thyroid stimulating immunoglobulins has been studied in twenty-two patients with Graves' disease. The thyroid stimulating immunoglobulins were assessed by parallel measurements of thyrotrophin receptor binding inhibitory immunoglobulins (TBII) and of thyroid adenylate cyclase stimulating immunoglobulins (TACSI) in serum by radioreceptor assay and stimulation of adenylate cyclase respectively. The present study thus confirms that radioiodine therapy is followed by an increase of TBII and TACSI in most patients with Graves' disease. The level of TBII can probably provide a marker for development of hypothyroidism following 131 I therapy and might be involved in its pathogenesis. (author)

  5. Use of intravenous immunoglobulin in neonates with haemolytic disease and immune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Marković-Sovtić Gordana

    2013-01-01

    Full Text Available Background/Aim. Intravenous immunoglobulin is a blood product made of human polyclonal immunoglobulin G. The mode of action of intravenous immunoglobulin is very complex. It is indicated in treatment of neonatal immune thrombocytopenia and haemolytic disease of the newborn. The aim of the study was to present our experience in the use of intravenous immunoglobulin in a group of term neonates. Methods. We analysed all relevant clinical and laboratory data of 23 neonates who recieved intravenous immunoglobulin during their hospitalization in Neonatal Intensive Care Unit of Mother and Child Health Care Institute over a five year period, from 2006. to 2010. Results. There were 11 patients with haemolytic disease of the newborn and 12 neonates with immune thrombocytopenia. All of them recieved 1-2 g/kg intravenous immunoglobulin in the course of their treatment. There was no adverse effects of intravenous immunoglobulin use. The use of intravenous immunoglobulin led to an increase in platelet number in thrombocytopenic patients, whereas in those with haemolytic disease serum bilirubin level decreased significantly, so that some patients whose bilirubin level was very close to the exchange transfusion criterion, avoided this procedure. Conclusion. The use of intravenous immunoglobulin was shown to be an effective treatment in reducing the need for exchange transfusion, duration of phototherapy and the length of hospital stay in neonates with haemolytic disease. When used in treatment of neonatal immune thrombocytopenia, it leads to an increase in the platelet number, thus decreasing the risk of serious complications of thrombocytopenia.

  6. Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes

    International Nuclear Information System (INIS)

    Grayson, J.; Dooley, N.J.; Koski, I.R.; Blaese, R.M.

    1981-01-01

    The direct effects of steroid hormones on the production of immunoglobulins and DNA synthesis by human T and B lymphocytes was evaluated in cultures of peripheral blood mononuclear cells. As detected by a reverse hemolytic plaque assay, the addition of 0.1 mM to 10 nM hydrocortisone to lymphocytes in culture in the absence of other stimulants or mitogens, resulted in the dramatic induction of immunoglobulin production with responses comparable to those seen in similar cultures stimulated with pokeweed mitogen. Steroid-stimulated immunoglobulin production was first seen after 48 h and peaked at 8-10 d of culture. The production of IgG, IgA, and IgM was induced following incubation with steroid. Glucocorticoids, but not estrogens or androgens, were capable of mediating this effect, and only compounds with affinity for the glucocorticoid receptor were active. The induction of immunoglobulin production was dependent on both T cells and monocytes; cultures depleted of either cell type did not produce immunoglobulin when stimulated with glucocorticoid hormones. Proliferation of B cells or T cells could not be detected by [/sup 3/H]thymidine incorporation or total cell recovery from steroid-stimulated cultures, even though such cultures demonstrated marked increases in immunoglobulin production. The mechanism responsible for this functional maturation of B cells to become high rate immunoglobulin producing cells is as yet undefined, although it appears to involve more than merely steroid mediated inactivation of suppressor T cells

  7. Falsely Elevated Plasma Creatinine Due to an Immunoglobulin M Paraprotein.

    Science.gov (United States)

    McGill, Mitchell R; Vijayan, Anitha; Trulock, Elbert P; Witt, Chad A; Kohler, Giselle D; Scott, Mitchell G

    2016-11-01

    The most common method for measuring plasma creatinine is based on its reaction with picric acid. However, enzymatic methods are becoming more popular due to improved specificity. We present a case of falsely elevated plasma creatinine values obtained by an enzymatic method that turned out to be due to a monoclonal immunoglobulin M (IgM) paraprotein. A 63-year-old woman evaluated for lung transplantation had falsely increased plasma creatinine levels (1.54-1.71mg/dL; corresponding to estimated glomerular filtration rates of 32-36 mL/min/1.73m 2 ) as measured by the Roche Creatinine plus enzymatic assay when compared with the picric acid-based procedure and several other enzymatic methods, which gave plasma creatinine values of 0.7 to 0.8mg/dL. Serum protein electrophoresis revealed an IgM κ light chain paraprotein. Removal of high-molecular-weight (>30kDa) proteins by ultrafiltration reduced the patient's plasma creatinine level by the Roche enzymatic method to 0.7mg/dL. Addition of the patient's immunoglobulin fraction to plasma from other patients with normal plasma creatinine levels resulted in values that were increased by 0.58 to 0.62mg/dL. Furthermore, removal of non-IgM immunoglobulins with protein G-coupled beads did not eliminate the interference from the patient's plasma. Taken together, these studies demonstrate that falsely elevated plasma creatinine values by the Roche enzymatic method can be due to an IgM paraprotein. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  8. Differentiating immunoglobulin g4-related sclerosing cholangitis from hilar cholangiocarcinoma.

    Science.gov (United States)

    Tabata, Taku; Kamisawa, Terumi; Hara, Seiichi; Kuruma, Sawako; Chiba, Kazuro; Kuwata, Go; Fujiwara, Takashi; Egashira, Hideto; Koizumi, Koichi; Fujiwara, Junko; Arakawa, Takeo; Momma, Kumiko; Kurata, Masanao; Honda, Goro; Tsuruta, Koji; Itoi, Takao

    2013-03-01

    Few studies have differentiated immunoglobulin G (IgG) 4-related sclerosing cholangitis (IgG4-SC) from hilar cholangiocarcinoma (CC). Thus, we sought to investigate useful features for differentiating IgG4-SC from hilar CC. We retrospectively compared clinical, serological, imaging, and histological features of six patients with IgG4-SC and 42 patients with hilar CC. In patients with hilar CC, obstructive jaundice was more frequent (philar CC patients (philar or hepatic duct was completely obstructed in 83% of hilar CC patients (philar bile duct stenosis, was more frequent in IgG4-SC patients (philar CC.

  9. Immunoglobulin G for patients with necrotising soft tissue infection (INSTINCT)

    DEFF Research Database (Denmark)

    Madsen, Martin B.; Hjortrup, Peter B.; Hansen, Marco B.

    2017-01-01

    Purpose: The aim of the INSTINCT trial was to assess the effect of intravenous polyspecific immunoglobulin G (IVIG) compared with placebo on self-reported physical function in intensive care unit (ICU) patients with necrotising soft tissue infection (NSTI). Methods: We randomised 100 patients...... with NSTI 1:1 to masked infusion of 25 g of IVIG (Privigen, CSL Behring) or an equal volume of 0.9% saline once daily for the first 3 days of ICU admission. The primary outcome was the physical component summary (PCS) score of the 36-item short form health survey (SF-36) 6 months after randomisation...

  10. Use of [75Se]selenomethionine in immunoglobulin biosynthetic studies

    International Nuclear Information System (INIS)

    Gutman, G.A.; Warner, N.L.; Harris, A.W.; Bowles, A.

    1978-01-01

    The gamma-emitting amino acid analog, [ 75 Se] selenomethionine, has been used as a biosynthetic label for immunoglobulins secreted by plasmacytomas in tissue culture. The secreted products are structurally intact with respect to their antibody combining sites and their class and allotype antigenic specificities. A component of [ 75 Se] selenomethionine preparations was found to bind to fetal calf serum proteins, in a manner releasable by mercaptoethanol, but not by sodium dodecyl sulfate and urea. Methods for circumventing the problems caused by this binding are described. (Auth.)

  11. Malacoplakia associated with vesicoureteral reflux and selective immunoglobulin A deficiency.

    Science.gov (United States)

    Witherington, R; Branan, W J; Wray, B B; Best, G K

    1984-11-01

    A case of malacoplakia involving the lower urinary tract of a young black boy, with associated bilateral vesicoureteral reflux, hydronephrosis and selective immunoglobulin A deficiency is reported. Reflux was caused by the malacoplakia. Reflux and hydronephrosis persisted despite elimination of bacterial infection and malacoplakia by drug therapy. These abnormalities were corrected by a conventional antireflux operation. Malacoplakia appears to be related to immunologic incompetence and diminished levels of intracellular cyclic 3',5' guanine monophosphate. Cholinergic agonists reverse or prevent the pathological changes of malacoplakia.

  12. Immunoglobulin Concentration in Tears of Contact Lens Wearers

    Science.gov (United States)

    Maurya, Rajendra P.; Bhushan, Prashant; Singh, Virendra P.; Singh, Mahendra K.; Kumar, Prakash; Bhatia, Ravindra P.S.; Singh, Usha

    2014-01-01

    Purpose: To evaluate changes in the concentration of tear immunoglobulins in contact lens wearers. Methods: A total of 45 cases including 23 contact lens wearers (43 eyes) and 22 age and sex matched healthy controls having no ocular pathology were studied for immunoglobulins (IgA, IgG, IgM) in their tears by single radial immunodiffusion method. Results: Most of the cases used soft (56.6%) and semi-soft gas permeable (30.4%) contact lenses. Tear IgM was detected in only 17.4% and tear IgG in 43.6% of contact lens wearers, while in controls IgG was detected in 9.1% but none of the controls had IgM. There was a significant rise in total tear IgA (13.17 ± 4.44 mg/dl) in contact lens wearer as compared to controls (8.93 ± 3.79 mg/dl). Rise of tear IgA was more in symptomatic patients (15.38 ± 5.28 mg/dl) and in those wearing hard (19.73 ± 5.43 mg/dl) and semi-soft contact lenses (13.31 ± 5.43 mg/dl). A significant increase in tear IgA was noticed in subjects wearing lenses for >3 years (15.69 ± 5.39 mg/dl). About 43.4% of lens wearers were symptomatic and 80% of their lenses showed deposits and/or haziness. All cases with IgM in tear were symptomatic. Conclusion: The relation of immunoglobulin concentration with increasing duration of wear and material of contact lens shows that tear immunoglobulin rise accrues due to mechanical stimulation, hence contact lenses should not be used for a long period and lenses of hard nature should be discouraged. The maintenance, cleaning and deproteinization of the lenses are of high importance to avoid immunostimulation. PMID:25667732

  13. INFLUENCE OF HIGH CORTISOL DOSES UPON THE SERUM IMMUNOGLOBULIN LEVEL

    OpenAIRE

    Voja Pavlovic; Zoran Pavlovic

    2001-01-01

    The effects of Cortisol upon the serum immunoglobulin concentration areexamined. The experiment involved male guinea pigs of the body weight from 300 to400 g that were nonnally fed and lived under the common laboratory conditions. Theguinea pigs were divided into an experimental and a control group. The experimentalgroup's guinea pigs were given every day (in a 6 days' period) a subcutaneous dose of80 g of corti sol/kg/per day, while the control group ones were given only one ml ofthe physiol...

  14. Grave's disease associated with immunoglobulin A nephropathy: A rare association.

    Science.gov (United States)

    Khan, I; Bhat, R A; Khan, I; Hameed, I

    2015-01-01

    Immunoglobulin A (Ig A) nephropathy is the most common form of primary glomerulonephritis. The association of Ig A nephropathy with Grave's disease has not been reported so far. We report a case of 20-year-old female with Grave's disease who presented with edema, facial puffiness, and decreased urine output. She was found to be hypertensive with renal failure and nephrotic range proteinuria. Renal biopsy revealed features of Ig A nephropathy. The patient was treated with oral corticosteroids (1 mg/kg/day). To our knowledge, this is the first case showing association of Grave's disease with Ig A nephropathy.

  15. Evaluation of adsorption selectivity of immunoglobulins M, A and G and purification of immunoglobulin M with mixed-mode resins.

    Science.gov (United States)

    Luo, Ying-Di; Zhang, Qi-Lei; Yao, Shan-Jing; Lin, Dong-Qiang

    2018-01-19

    This study investigated adsorption selectivity of immunoglobulin M (IgM), immunoglobulin A (IgA) and immunoglobulin (IgG) on four mixed-mode resins with the functional ligands of 4-mercatoethyl-pyridine (MEP), 2-mercapto-1-methylimidazole (MMI), 5-aminobenzimidazole (ABI) and tryptophan-5-aminobenzimidazole (W-ABI), respectively. IgM purification processes with mixed-mode resins were also proposed. All resins showed typical pH-dependent adsorption, and high adsorption capacity was found at pH 5.0-8.0 with low adsorption capacity under acidic conditions. Meanwhile, high selectivity of IgM/IgA and IgM/IgG was obtained with ABI-4FF and MMI-4FF resins at pH 4.0-5.0, which was used to develop a method for IgM, IgA and IgG separation by controlling loading and elution pH. Capture of monoclonal IgM from cell culture supernatant with ABI-4FF resins was studied and high purity (∼99%) and good recovery (80.8%) were obtained. Moreover, IgM direct separation from human serum with combined two-step chromatography (ABI-4FF and MMI-4FF) was investigated, and IgM purity of 65.2% and a purification factor of 28.3 were obtained after optimization. The antibody activity of IgM was maintained after purification. The results demonstrated that mixed-mode chromatography with specially-designed ligands is a promising way to improve adsorption selectivity and process efficiency of IgM purification from complex feedstock. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Immunoglobulins in the eggs of the nurse shark, Ginglymostoma cirratum.

    Science.gov (United States)

    Haines, Ashley N; Flajnik, Martin F; Rumfelt, Lynn L; Wourms, John P

    2005-01-01

    Elasmobranchs, which include the sharks, skates, and rays, emerged over 450 million years ago and are the oldest vertebrates to possess an adaptive immune system. They have evolved diverse reproductive modes, with a variety of physiological adaptations that enhance reproductive success. The nurse shark, Ginglymostoma cirratum, is an aplacental, viviparous elasmobranch in which the egg and its associated vitelline vasculature are the primary route for maternal-embryonic interactions. During gestation, nurse shark embryos hatch from their eggcases and develop free in the uterus, which is flushed regularly with seawater. Similar to higher vertebrates, embryonic and neonatal nurse sharks possess an immune system that is not fully competent. In birds and bony fishes, maternal immunoglobulins (Ig) stored in the egg during oogenesis confer protective immunity to embryos during gestation. However, early research suggested that such transfer of passive immunity does not occur in sharks. To better understand how elasmobranch embryos are protected from waterborne pathogens during this potentially vulnerable time, we have re-examined the existence of Igs in elasmobranch eggs. Using monoclonal antibodies, we establish the presence of two classes of Igs in nurse shark eggs: 7S IgM and IgNAR. The potential transfer of immunoglobulins from elasmobranch eggs is discussed.

  17. Immunoglobulins and C3 in the P. brasiliensis granuloma

    Directory of Open Access Journals (Sweden)

    Lilian M. V. Biagioni

    1987-04-01

    Full Text Available The experimental model of paracoccidioidomycosis induced in mice by the intravenous injection of yeast-forms of P. brasiliensis (Bt2 strain; 1 x 10(6 viable fungi/animal was used to evaluate sequentially 2, 4, 8, 16 and 20 weeks after inoculation: 1. The presence of immunoglobulins and C3 in the pulmonary granuloma-ta, by direct immunofluorescence; 2. The humoral (immunodiffusion test and the cellular (footpad sweeling test immune response; 3. The histopathology of lesions. The cell-immune response was positive since week 2, showing a transitory depression at week 16. Specific antibodies were first detected at week 4 and peaked at week 16. At histology, epithelioid granulomas with numerous fungi and polymorphonuclear agreggates were seen. The lungs showed progressive involvement up to week 16, with little decrease at week 20. From week 2 on, there were deposits of IgG and C3 around fungal walls within the granulomas and IgG stained cells among the mononuclear cell peripheral halo. Interstitital immunoglobulins and C3 deposits in the granulomas were not letected. IgG and C3 seen to play an early an important role in. the host defenses against P. brasiliensis by possibly cooperating in the killing of parasites and blocking the antigenic diffusion.

  18. Autoantibodies and immunoglobulins among atomic-bomb survivors

    International Nuclear Information System (INIS)

    Fujiwara, Saeko; Carter, R.L.; Akiyama, Mitoshi

    1993-06-01

    The purpose of this study was to determine if exposure to atomic-bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody, and immunoglobulin levels (IgG, IgM, IgA, and IgE) were measured among 2061 Adult Health Study participants in Hiroshima and Nagasaki from December 1987 to November 1989. The prevalence and titers of rheumatoid factor increased in a statistically significant manner with increasing radiation dose. No radiation effect was found on the prevalence of antinuclear antibody, antithyroglobulin antibody, and anti-thyroid-microsomal antibody. A statistically significant relationship was also found between radiation exposure and the IgA level in females and the IgM levels in both sexes-both levels increased as radiation dose increased. However, the effects of radiation exposure were not large and accounted for less than 10% of the total variation in each measurement. Levels of IgG and IgE were not affected by radiation exposure. (author)

  19. Risk factors for venous thromboembolism in immunoglobulin light chain amyloidosis.

    Science.gov (United States)

    Bever, Katherine M; Masha, Luke I; Sun, Fangui; Stern, Lauren; Havasi, Andrea; Berk, John L; Sanchorawala, Vaishali; Seldin, David C; Sloan, J Mark

    2016-01-01

    Patients with immunoglobulin light chain amyloidosis are at risk for both thrombotic and bleeding complications. While the hemostatic defects have been extensively studied, less is known about thrombotic complications in this disease. This retrospective study examined the frequency of venous thromboembolism in 929 patients with immunoglobulin light chain amyloidosis presenting to a single referral center, correlated risk of venous thromboembolism with clinical and laboratory factors, and examined complications of anticoagulation in this population. Sixty-five patients (7%) were documented as having at least one venous thromboembolic event. Eighty percent of these patients had events within one year prior to or following diagnosis. Lower serum albumin was associated with increased risk of VTE, with a hazard ratio of 4.30 (CI 1.60-11.55; P=0.0038) for serum albumin less than 3 g/dL compared to serum albumin greater than 4 g/dL. Severe bleeding complications were observed in 5 out of 57 patients with venous thromboembolism undergoing treatment with anticoagulation. Prospective investigation should be undertaken to better risk stratify these patients and to determine the optimal strategies for prophylaxis against and management of venous thromboembolism. Copyright© Ferrata Storti Foundation.

  20. Cytomegalovirus neutralization by hyperimmune and standard intravenous immunoglobulin preparations.

    Science.gov (United States)

    Planitzer, Christina B; Saemann, Marcus D; Gajek, Hartwig; Farcet, Maria R; Kreil, Thomas R

    2011-08-15

    Cytomegalovirus (CMV) remains one of the most important pathogens after transplantation, potentially leading to CMV disease, allograft dysfunction, acute, and chronic rejection and opportunistic infections. Immunoglobulin G (IgG) preparations with high antibody titers against CMV are a valuable adjunctive prevention and treatment option for clinicians and apart from standard intravenous immunoglobulin (IVIG), CMV hyperimmune preparations are available. The CMV antibody titer of these preparations is typically determined by Enzyme-linked immunosorbent assay (ELISA), also used for the selection of high titer plasma donors for the production of the CMV Hyperimmune product. However, CMV ELISA titers do not necessarily correlate with CMV antibody function which is determined by virus neutralization tests. CMV antibody titers were determined by both ELISA and virus neutralization assay and the IgG subclass distribution was compared between a CMV hyperimmune licensed in Europe and standard IVIG preparations. Although the expected high CMV IgG ELISA antibody titers were confirmed for three lots of a CMV hyperimmune preparation, the functionally more relevant CMV neutralizing antibody titers were significantly higher for 31 lots of standard IVIG preparations. Moreover, considerably lower IgG3 levels were found for the CMV hyperimmune preparation compared with standard IVIG preparations. The higher functional CMV neutralization titers of standard IVIG preparations and the better availability of these preparations, suggest that these products could be a valuable alternative to the CMV hyperimmune preparation.

  1. Risk factors for venous thromboembolism in immunoglobulin light chain amyloidosis

    Science.gov (United States)

    Bever, Katherine M.; Masha, Luke I.; Sun, Fangui; Stern, Lauren; Havasi, Andrea; Berk, John L.; Sanchorawala, Vaishali; Seldin, David C.; Sloan, J. Mark

    2016-01-01

    Patients with immunoglobulin light chain amyloidosis are at risk for both thrombotic and bleeding complications. While the hemostatic defects have been extensively studied, less is known about thrombotic complications in this disease. This retrospective study examined the frequency of venous thromboembolism in 929 patients with immunoglobulin light chain amyloidosis presenting to a single referral center, correlated risk of venous thromboembolism with clinical and laboratory factors, and examined complications of anticoagulation in this population. Sixty-five patients (7%) were documented as having at least one venous thromboembolic event. Eighty percent of these patients had events within one year prior to or following diagnosis. Lower serum albumin was associated with increased risk of VTE, with a hazard ratio of 4.30 (CI 1.60–11.55; P=0.0038) for serum albumin less than 3 g/dL compared to serum albumin greater than 4 g/dL. Severe bleeding complications were observed in 5 out of 57 patients with venous thromboembolism undergoing treatment with anticoagulation. Prospective investigation should be undertaken to better risk stratify these patients and to determine the optimal strategies for prophylaxis against and management of venous thromboembolism. PMID:26452981

  2. Killer Immunoglobulin-Like Receptor Allele Determination Using Next-Generation Sequencing Technology

    Directory of Open Access Journals (Sweden)

    Bercelin Maniangou

    2017-05-01

    Full Text Available The impact of natural killer (NK cell alloreactivity on hematopoietic stem cell transplantation (HSCT outcome is still debated due to the complexity of graft parameters, HLA class I environment, the nature of killer cell immunoglobulin-like receptor (KIR/KIR ligand genetic combinations studied, and KIR+ NK cell repertoire size. KIR genes are known to be polymorphic in terms of gene content, copy number variation, and number of alleles. These allelic polymorphisms may impact both the phenotype and function of KIR+ NK cells. We, therefore, speculate that polymorphisms may alter donor KIR+ NK cell phenotype/function thus modulating post-HSCT KIR+ NK cell alloreactivity. To investigate KIR allele polymorphisms of all KIR genes, we developed a next-generation sequencing (NGS technology on a MiSeq platform. To ensure the reliability and specificity of our method, genomic DNA from well-characterized cell lines were used; high-resolution KIR typing results obtained were then compared to those previously reported. Two different bioinformatic pipelines were used allowing the attribution of sequencing reads to specific KIR genes and the assignment of KIR alleles for each KIR gene. Our results demonstrated successful long-range KIR gene amplifications of all reference samples using intergenic KIR primers. The alignment of reads to the human genome reference (hg19 using BiRD pipeline or visualization of data using Profiler software demonstrated that all KIR genes were completely sequenced with a sufficient read depth (mean 317× for all loci and a high percentage of mapping (mean 93% for all loci. Comparison of high-resolution KIR typing obtained to those published data using exome capture resulted in a reported concordance rate of 95% for centromeric and telomeric KIR genes. Overall, our results suggest that NGS can be used to investigate the broad KIR allelic polymorphism. Hence, these data improve our knowledge, not only on KIR+ NK cell alloreactivity in

  3. 21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

    Science.gov (United States)

    2010-04-01

    ... of antibody-forming cells), lymphocytic neoplasms (cancer of lymphoid tissue), Waldenstrom's macroglobulinemia (increased production of large immunoglobulins), and connective tissue diseases such as rheumatoid... portions of immunoglobulin molecules in serum, other body fluids, and tissues. In some disease states, an...

  4. Characterization of immunoglobulin A kappa autoantibodies to human lactate dehydrogenase isoenzyme-3

    NARCIS (Netherlands)

    Weijers, R. N.; Oude Elferink, R. P.; Mulder, J.; Kruijswijk, H.

    1987-01-01

    We have purified with a cumulative recovery of 48% from the serum of a patient the immunoglobulin A kappa subunit of the lactate dehydrogenase-immunoglobulin A kappa (LD-IgA kappa) complex. It appears that the pI range of the complex is 5.4-5.8. The Ig part of the complex showed a monoclonal

  5. Evaluation of immunoglobulin G synthesizing plasma cells in periapical granuloma and cyst.

    OpenAIRE

    Grover N; Rao N; Kotian M

    2001-01-01

    Immunoglobulin synthesizing plasma cells for IgG were quantitated in 20 periapical granulomas and 20 periapical cysts, using unlabelled antibody peroxidase-antiperoxidase complex method. Result showed that immunoglobulin G producing plasma cells were predominant in periapical cyst as compared with periapical granuloma. A statistical significant relation was observed between these two lesions.

  6. Breakpoint of an inversion of chromosome 14 in a T-cell leukemia: sequences downstream of the immunoglobulin heavy chain locus are implicated in tumorigenesis

    International Nuclear Information System (INIS)

    Baer, R.; Heppell, A.; Taylor, A.M.R.; Rabbitts, P.H.; Boullier, B.; Rabbitts, T.H.

    1987-01-01

    T-cell tumors are characterized by inversions or translocations of chromosome 14. The breakpoints of these karyotypic abnormalities occur in chromosome bands 14q11 and 14q32 - the same bands in which the T-cell receptor (TCR) α-chain and immunoglobulin heavy chain genes have been mapped, respectively. Patients with ataxia-telangiectasia are particularly prone to development of T-cell chronic lymphocytic leukemia with such chromosomal abnormalities. The authors describe DNA rearrangements of the TCR α-chain gene in an ataxia-telangiectasia-associated leukemia containing both a normal and an inverted chromosome 14. The normal chromosome 14 has undergone a productive join of TCR α-chain variable (V/sub α/) and joining (J/sub α/) gene segments. The other allele of the TCR α-chain gene features a DNA rearrangement, about 50 kilobases from the TCR α-chain constant (C/sub α/) gene, that represents the breakpoint of the chromosome 14 inversion; this breakpoint is comprised of a TCR J/sub α/) segment (from 14q11) fused to sequences derived from 14q32 but on the centromeric side of C/sub μ/. These results imply that 14q32 sequences located at an undetermined distance downstream of immunoglobulin C/sub μ/ locus can contribute to the development of T-cell tumors

  7. Circulating immune complexes, immunoglobulin G, salivary proteins and salivary immunoglobulin A in patients with Sjögren's syndrome

    Directory of Open Access Journals (Sweden)

    Hadži-Mihailović Miloš

    2009-01-01

    Full Text Available Introduction. Sjögren's syndrome (SS is a chronic autoimmune disorder, with its major clinical manifestations resulting from changes in exocrine glands. Objective The aim of this study was to evaluate serum concentrations of circulating immune complexes (CIC and immunoglobulin G (IgG, and salivary proteins (SP and salivary immunoglobulin A (sIgA in 40 patients with SS, and to correlate these values among themselves, as well as with the unstimulated salivary flow rate (USFR and the duration of disease. Methods. The total of 40 patients were included in this research. CIC was determined using the solution of polyethylene glycol and IgG with the standard procedure of radial immunodiffusion. SP was investigated by the method of Lowry and sIgA was separated from the whole saliva using the method of immune chromatography. Results. The values of most of the studied parameters exceeded the normal range in a high degree: CIC 72.5%, IgG 70%, SP 80%. The concentrations of CIC were significantly higher in the patients with the duration of disease less than 10 years. With the decrease of USFR, the concentration of sIgA and IgG were increased with statistical significance. Conclusion The increased prevalence of abnormal values of CIC, IgG and SP indicate that the patients with SS have developed a higher level of immune reactivity. These results could be useful in diagnosis and disease activity monitoring.

  8. A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

    International Nuclear Information System (INIS)

    Sui, Weiguo; Che, Wenti; Guimai, Zuo; Chen, Jiejing; Li, Liping; Li, Wuxian; Dai, Yong

    2012-01-01

    Objectives: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. Methods: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. Results: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-inositol, lactate, L6 lipids ( CH-CH 2 -CH = O), L5 lipids (-CH 2 -C = O), and L3 lipids (-CH 2 -CH 2 -C = O) as well as lower levels of β-glucose, α-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. Conclusions: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high-risk groups in our research

  9. A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Weiguo; Che, Wenti; Guimai, Zuo; Chen, Jiejing [181st Hospital Guangxi, Central Laboratory, Laboratory of Metabolic Diseases Research, Guangxi Province (China); Li, Liping [Guangxi Normal University, The Life Science College, Guangxi Province (China); Li, Wuxian [Key Laboratory of Laboratory Medical Diagnostics of Education Ministry, Chongqiong Medical University, Chongqing (China); Dai, Yong [Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People' s Hospital), Shenzhen, Guangdong Province (China)

    2012-07-01

    Objectives: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. Methods: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. Results: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-inositol, lactate, L6 lipids ( CH-CH{sub 2}-CH = O), L5 lipids (-CH{sub 2}-C = O), and L3 lipids (-CH{sub 2}-CH{sub 2}-C = O) as well as lower levels of {beta}-glucose, {alpha}-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. Conclusions: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high

  10. Melanophore migration and survival during zebrafish adult pigment stripe development require the immunoglobulin superfamily adhesion molecule Igsf11.

    Science.gov (United States)

    Eom, Dae Seok; Inoue, Shinya; Patterson, Larissa B; Gordon, Tiffany N; Slingwine, Rebecca; Kondo, Shigeru; Watanabe, Masakatsu; Parichy, David M

    2012-01-01

    The zebrafish adult pigment pattern has emerged as a useful model for understanding the development and evolution of adult form as well as pattern-forming mechanisms more generally. In this species, a series of horizontal melanophore stripes arises during the larval-to-adult transformation, but the genetic and cellular bases for stripe formation remain largely unknown. Here, we show that the seurat mutant phenotype, consisting of an irregular spotted pattern, arises from lesions in the gene encoding Immunoglobulin superfamily member 11 (Igsf11). We find that Igsf11 is expressed by melanophores and their precursors, and we demonstrate by cell transplantation and genetic rescue that igsf11 functions autonomously to this lineage in promoting adult stripe development. Further analyses of cell behaviors in vitro, in vivo, and in explant cultures ex vivo demonstrate that Igsf11 mediates adhesive interactions and that mutants for igsf11 exhibit defects in both the migration and survival of melanophores and their precursors. These findings identify the first in vivo requirements for igsf11 as well as the first instance of an immunoglobulin superfamily member functioning in pigment cell development and patterning. Our results provide new insights into adult pigment pattern morphogenesis and how cellular interactions mediate pattern formation.

  11. Melanophore migration and survival during zebrafish adult pigment stripe development require the immunoglobulin superfamily adhesion molecule Igsf11.

    Directory of Open Access Journals (Sweden)

    Dae Seok Eom

    Full Text Available The zebrafish adult pigment pattern has emerged as a useful model for understanding the development and evolution of adult form as well as pattern-forming mechanisms more generally. In this species, a series of horizontal melanophore stripes arises during the larval-to-adult transformation, but the genetic and cellular bases for stripe formation remain largely unknown. Here, we show that the seurat mutant phenotype, consisting of an irregular spotted pattern, arises from lesions in the gene encoding Immunoglobulin superfamily member 11 (Igsf11. We find that Igsf11 is expressed by melanophores and their precursors, and we demonstrate by cell transplantation and genetic rescue that igsf11 functions autonomously to this lineage in promoting adult stripe development. Further analyses of cell behaviors in vitro, in vivo, and in explant cultures ex vivo demonstrate that Igsf11 mediates adhesive interactions and that mutants for igsf11 exhibit defects in both the migration and survival of melanophores and their precursors. These findings identify the first in vivo requirements for igsf11 as well as the first instance of an immunoglobulin superfamily member functioning in pigment cell development and patterning. Our results provide new insights into adult pigment pattern morphogenesis and how cellular interactions mediate pattern formation.

  12. Immunoassay of serum polypeptide hormones by using 125I-labelled anti(-immunoglobulin G) antibodies.

    Science.gov (United States)

    Beck, P; Nicholas, H

    1975-03-01

    1. A technique for indirectly labelling antibodies to polypeptide hormones, by combining them with radioactively labelled anti-(immunoglobulin G) is described. (a) 125I-labelled anti-(rabbit immunoglobulin G) and anti-(guinea-pig immunoglobulin G) antibodies with high specific radioactivity were prepared after purification of the antibodies on immunoadsorbents containing the respective antigens. (b) Rabbit immunoglobulin G antibodies to human growth hormone, porcine glucagon and guinea-pig immunoglobulin G antibodies to bovine insulin and bovine parathyroid hormone were combined with immunoadsorbents containing the respective polypeptide hormone antigen. (c) The immunoglobulin G antibodies to the polypeptide hormones were reacted with 125-I-labelled anti-(immunoglobulin G) antibodies directed against the appropriate species of immunoglobulin G,and the anti-hormone antibodies were combined with the hormone-containing immunoadsorbent. (d) 125I-labelled anti-(immunoglobulin G) antibodies and anti-hormone antibodies were simultaneously eluted from the hormone-containing immunoadsorbent by dilute HCl, pH 2.0. After elution the anti-(immunoglobulin G) antibodies and antihormone antibodies were allowed to recombine at pH 8.0 and 4 degrees C. 2. The resultant immunoglobulin G-anti-immunoglobulin G complex was used in immunoradiometric (labelled antibody) and two-site assays of the respective polypeptide hormone. 3. By using these immunoassays, concentrations down to 90pg of human growth hormone/ml, 100 pg of bovine insulin/ml, 80 pg of bovine parathyroid hormone/ml and 150 pg of glucagon/ml were readily detected. Assays of human plasma for growth hormone and insulin by these methods showed good agreement with results obtained by using a directly 125I-labelled anti-hormone antibody in an immunoradiometric assay of human growth hormone or by radioimmunoassay of human insulin. 4. The method described allows immunoradiometric or two-site assays to be performed starting with as

  13. Subcutaneous immunoglobulin preserves muscle strength in chronic inflammatory demyelinating polyneuropathy

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Harbo, Thomas; Sindrup, Søren Hein

    2014-01-01

    evaluated after 3, 6 and 12 months. Primary end-points were changes in muscle strength evaluated by isokinetic dynamometry in four affected muscle groups and a composite score of muscle performance and function tests, including Medical Research Council (MRC) score, grip strength, 40-m walking test (40-MWT......BACKGROUND AND PURPOSE: Subcutaneous immunoglobulin (SCIG) is superior to placebo treatment for maintenance of muscle strength during 12 weeks in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The present study evaluated whether SCIG preserves muscle strength for 1 year......) and nine-hole peg test (9-HPT). Secondary end-points were changes of each of the listed parameters at each time point as well as an overall disability sum score (ODSS). RESULTS: The dose of SCIG was significantly unaltered during the follow-up period. Overall the isokinetic dynamometry value increased by 7...

  14. Immunoglobulin subclass in experimental murine Toxocara cati infection

    Directory of Open Access Journals (Sweden)

    Kusnoto

    2017-11-01

    Full Text Available Aim: The aim of this study was to detect specific immunoglobulin (Ig that could be used to determine monoclonal antibody in conjugate-making an effort for the indirect enzyme-linked immunosorbent assay (ELISA diagnostic kit of toxocariasis in human. Materials and Methods: The study was conducted to assess the Ig profile, based on ELISA-isotyping, in mice infected with second stage larvae eggs of Toxocara cati. The optical density values of anti-T. cati mice serum IgG subclasses were analyzed by applying ANOVA factorial. Results: The specific IgG subclass in mice infected with T. cati mice was found to be IgG2β. Conclusion: Subclass of IgG, especially IgG2β, can provide leads about the use of the monoclonal antibody in conjugate making an effort for the indirect ELISA diagnostic kit.

  15. Antibody structural modeling with prediction of immunoglobulin structure (PIGS)

    DEFF Research Database (Denmark)

    Marcatili, Paolo; Olimpieri, Pier Paolo; Chailyan, Anna

    2014-01-01

    Antibodies (or immunoglobulins) are crucial for defending organisms from pathogens, but they are also key players in many medical, diagnostic and biotechnological applications. The ability to predict their structure and the specific residues involved in antigen recognition has several useful...... applications in all of these areas. Over the years, we have developed or collaborated in developing a strategy that enables researchers to predict the 3D structure of antibodies with a very satisfactory accuracy. The strategy is completely automated and extremely fast, requiring only a few minutes (∼10 min...... on average) to build a structural model of an antibody. It is based on the concept of canonical structures of antibody loops and on our understanding of the way light and heavy chains pack together....

  16. Intravenous Immunoglobulin in the Treatment of Primary Immunodeficiency Diseases.

    Science.gov (United States)

    De Ranieri, Deirdre; Fenny, Nana Sarkoah

    2017-01-01

    Intravenous immunoglobulin (IVIG) has been used as antibody replacement therapy in primary immunodeficiency diseases (PIDDs) for more than 50 years. Its role as a therapeutic agent has expanded over the past couple of decades as its anti-inflammatory and immune-modulatory mechanisms of action have been elucidated. It is now used "off-label" to treat other autoimmune diseases. This article focuses on the role of IVIG in the treatment of PIDDs characterized by absent or deficient antibody production. Replacement doses are given on a monthly basis in these conditions as a prophylactic measure to prevent acute and serious bacterial infections. [Pediatr Ann. 2017;46(1):e8-e12.]. Copyright 2017, SLACK Incorporated.

  17. Antibody structural modeling with prediction of immunoglobulin structure (PIGS)

    KAUST Repository

    Marcatili, Paolo

    2014-11-06

    © 2014 Nature America, Inc. All rights reserved. Antibodies (or immunoglobulins) are crucial for defending organisms from pathogens, but they are also key players in many medical, diagnostic and biotechnological applications. The ability to predict their structure and the specific residues involved in antigen recognition has several useful applications in all of these areas. Over the years, we have developed or collaborated in developing a strategy that enables researchers to predict the 3D structure of antibodies with a very satisfactory accuracy. The strategy is completely automated and extremely fast, requiring only a few minutes (~10 min on average) to build a structural model of an antibody. It is based on the concept of canonical structures of antibody loops and on our understanding of the way light and heavy chains pack together.

  18. Current clinical research of immunoglobulin G4-related orbital disease

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2016-05-01

    Full Text Available Immunoglobulin G4-related disease(IgG4-related diseasehas received lots of attention in medical community as a recently recognized fibro-inflammatory condition. It is characterized by infiltration of IgG4-immunopositive plasmacytes and concentration of elevated serum IgG4. IgG4-related disease shows organ enlargement or nodular/hyperplastic lesions in various organs including the pancreas, hepatobiliary tract and orbit, which is called IgG4-related orbital disease. The diagnostic criteria for IgG4-related disease and IgG4-related orbital disease has recently been established, which is based on clinical, imaging and histopathologic features of the orbital lesions. Besides, attention should be drawn to the differentiation from other diseases. The treatment is empirical including corticosteroids, immunosuppressive drugs, radiotherapy, and rituximab. This article reviews clinical progression of IgG4-related orbital disease.

  19. Serum immunoglobulin levels in atomic bomb survivors, Hiroshima

    Energy Technology Data Exchange (ETDEWEB)

    Hall, C B; Hall, W J; Ashley, F W; Hamilton, H B

    1972-01-01

    Serum immunoglobulins (SI) were determined in 803 survivors and matched controls. Each subject's age, sex, health, exposure, and medical record were evaluated with respect to serum IgG, IgA, IgM levels. The IgG and IgA levels tended to be higher for this Hiroshima population than for Americans. Past exposure to ionizing radiation showed no significant correlation to SI levels. However, age and sex did influence the SI. IgM was significantly higher in females. With advancing age IgG and IgA increased in males, and IgM decreased in females. Elevated sedimentation rate and increased lymphocytes were accompanied by increased SI levels. Radiographic TB was detected in 45% of the population; IgG and IgA levels were somewhat elevated in these individuals. (DLC)

  20. Intravenous immunoglobulin in ABO and Rh hemolytic diseases of newborn.

    Science.gov (United States)

    Nasseri, Fatemeh; Mamouri, Gholam A; Babaei, Homa

    2006-12-01

    To evaluate whether the use of intravenous immunoglobulin in newborn infants with isoimmune hemolytic jaundice due to Rh and ABO incompatibility is an effective treatment in reducing the need for exchange transfusion. This study included all direct Coombs' test positive Rh and ABO isoimmunized babies, who admitted in the Neonatal Intensive Care Unit of Ghaem Hospital of Mashhad University of Medical Sciences, Iran, from October 2003 to October 2004. Significant hyperbilirubinemia was defined as rising by >or=0.5 mg/dl per hour. Babies were randomly assigned to received phototherapy with intravenous immunoglobulin (IVIg) 0.5 g/kg over 4 hours, every 12 hours for 3 doses (study group) or phototherapy alone (control group). Exchange transfusion was performed in any group if serum bilirubin exceeded >or=20mg/dl or rose by >or=1mg/dl/h. A total of 34 babies were eligible for this study (17 babies in each group). The number of exchange transfusion, duration of phototherapy and hospitalization days, were significant shorter in the study group versus control group. When we analyzed the outcome results in ABO and Rh hemolytic disease separately, the efficacy of IVIg was significantly better in Rh versus ABO isoimmunization. Late anemia was more common in the IVIg group 11.8% versus 0%, p=0.48. Adverse effects were not observed during IVIg administration. Administration of IVIg to newborns with significant hyperbilirubinemia due to Rh hemolytic disease reduced the need for exchange transfusion but in ABO hemolytic disease there was no significant difference between IVIg and double surface blue light phototherapy.

  1. Secretory immunoglobulin purification from whey by chromatographic techniques.

    Science.gov (United States)

    Matlschweiger, Alexander; Engelmaier, Hannah; Himmler, Gottfried; Hahn, Rainer

    2017-08-15

    Secretory immunoglobulins (SIg) are a major fraction of the mucosal immune system and represent potential drug candidates. So far, platform technologies for their purification do not exist. SIg from animal whey was used as a model to develop a simple, efficient and potentially generic chromatographic purification process. Several chromatographic stationary phases were tested. A combination of two anion-exchange steps resulted in the highest purity. The key step was the use of a small-porous anion exchanger operated in flow-through mode. Diffusion of SIg into the resin particles was significantly hindered, while the main impurities, IgG and serum albumin, were bound. In this step, initial purity was increased from 66% to 89% with a step yield of 88%. In a second anion-exchange step using giga-porous material, SIg was captured and purified by step or linear gradient elution to obtain fractions with purities >95%. For the step gradient elution step yield of highly pure SIg was 54%. Elution of SIgA and SIgM with a linear gradient resulted in a step yield of 56% and 35%, respectively. Overall yields for both anion exchange steps were 43% for the combination of flow-through and step elution mode. Combination of flow-through and linear gradient elution mode resulted in a yield of 44% for SIgA and 39% for SIgM. The proposed process allows the purification of biologically active SIg from animal whey in preparative scale. For future applications, the process can easily be adopted for purification of recombinant secretory immunoglobulin species. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. [Correlation of serum IL-16, IL-18 levels and immunoglobulins in children with asthma].

    Science.gov (United States)

    Xue, Yi-Nan; Zou, Xian-De; Wu, Jia-Ling

    2006-02-01

    This study examined the changes of serum levels of interleukin (IL)-16, IL-18 and immunoglobulins and the correlation of serum IL-16, IL-18 levels and immunoglobulins in children with asthma and aimed to explore the role of IL-16, IL-18 and immunoglobulins in the pathogenesis of asthma. Thirty-four children with asthma and 21 age and gender-matched healthy children were enrolled in this study. The levels of IL-16, IL-18 and immunoglobulin E (IgE) were determined using ELISA. Immunoglobulin G (IgG), immunoglobulin M (IgM) and immunoglobulin A (IgA) were detected by immunoturbidimetry. The levels of IL-16, IL-18 and IgE in patients with asthma at both acute attack and convalescence stages were significantly higher than those in healthy controls. An increased IgG and a decreased IgA levels were found in asthmatic patients at the acute attack stage. There was a positive correlation between the IL-16 and IL-18 levels at both acute attack and convalescence stages of asthma (r=0.70, P attack stage of asthma (r=0.624, P asthma. The immunologic imbalance exists in children with asthma at both acute attack and convalescence stages. Anti-allergic therapy should be administered through the acute attack to the convalescence stages of asthma.

  3. Fragments of the constant region of immunoglobulin light chains are constituents of AL-amyloid proteins

    DEFF Research Database (Denmark)

    Olsen, K E; Sletten, K; Westermark, Per

    1998-01-01

    Immunoglobulin light chains are the precursor proteins of AL-amyloidosis. In the fibril formation process properties of the variable part of the immunoglobulin light chains are believed to be of major importance. In this work it is shown that fragments of the constant part of the immunoglobulin l...... light chain are a constituent of the AL-amyloid proteins of kappa type. A specific antiserum has identified these fragments in gel filtration fractions where the absorbance approached the base line after the main retarded peak. The fragments are small and have been overlooked previously......Immunoglobulin light chains are the precursor proteins of AL-amyloidosis. In the fibril formation process properties of the variable part of the immunoglobulin light chains are believed to be of major importance. In this work it is shown that fragments of the constant part of the immunoglobulin...... in the purification process. The significance of the constant part in AL-proteins is unclear, but adds new aspects to the discussion of pre- or post-fibrillogenic cleavage of the immunoglobulin light chains....

  4. Guanine is indispensable for immunoglobulin switch region RNA-DNA hybrid formation

    International Nuclear Information System (INIS)

    Mizuta, Ryushin; Mizuta, Midori; Kitamura, Daisuke

    2005-01-01

    It is suggested that the formation of the switch (S) region RNA-DNA hybrid and the subsequent generation of higher-order chromatin structures including R-loop initiate a class switch recombination of the immunoglobulin gene. The primary factor of this recombination is the S-region derived noncoding RNA. However, the biochemical character of this guanine-rich (G-rich) transcript is poorly understood. The present study was performed to analyze the structure of this G-rich RNA using atomic force microscope (AFM). The in vitro transcribed S-region RNA was spread on a mica plate, air-dried and observed by non-contact mode AFM in air. The G-rich transcripts tend to aggregate on the template DNA and to generate a higher-order RNA-DNA complex. However, the transcripts that incorporated guanine analogues as substitutes for guanine neither aggregated nor generated higher-order structures. Incorporation of guanine analogues in transcribes RNA partially disrupts hydrogen bonds related to guanine, such as Watson-Crick GC-base pair and Hoogsteen bond GG-base pair. Thus, aggregation of S-region RNA and generation of the higher-order RNA-DNA complex are attributed to hydrogen bonds of guanine. (author)

  5. Inhibition of neutrophil migration by aggregated immunoglobulin attached to micropore membranes.

    Science.gov (United States)

    Kemp, A S; Brown, S

    1980-01-01

    The effect of substrate-bound immunoglobulin on neutrophil migration was examined. Immunoglobulin aggregates bound to micropore membranes inhibited the neutrophil response to a chemotactic stimulus. This inhibition was reversed by the presence of aggregates in suspension suggesting competition between substrate-bound and free aggregates for neutrophil surface binding sites. The immobilization of neutrophils by substrate-bound aggregated immunoglobulin suggests a mechanism for the accumulation of neutrophils at sites of immune complex deposition and tissue-bound antibodies in vivo. PMID:7380477

  6. Swine plasma immunoglobulins for prevention and treatment of post-weaning diarrhoea: Safety and Preliminary results

    DEFF Research Database (Denmark)

    Hedegaard, Chris Juul; Strube, Mikael Lenz; Bendix Hansen, Marie

    . coli F4+ induced PWD, we observed that piglets given IgG as a feed supplement cleared the E coli infection significantly faster than control weaner piglets not receiving an immunoglobulin feed supplement. Furthermore, deep sequencing of the ileal microbiota showed a significantly lowered colonization...... their adhesion to porcine epithelial cells in vitro. As the immunoglobulin fraction is intended for oral use as a feed supplement, we also tested the safety of feeding 4 grams of natural immunoglobulins to 4-5 week old weaner piglets for 14 days and observed no adverse effects. In an experimental model of E...

  7. Idiotypes as immunogens: facing the challenge of inducing strong therapeutic immune responses against the variable region of immunoglobulins

    International Nuclear Information System (INIS)

    López-Requena, Alejandro; Burrone, Oscar R.; Cesco-Gaspere, Michela

    2012-01-01

    Idiotype (Id)-based immunotherapy has been exploited as cancer treatment option. Conceived as therapy for malignancies bearing idiotypic antigens, it has been also extended to solid tumors because of the capacity of anti-idiotypic antibodies to mimic Id-unrelated antigens. In both these two settings, efforts are being made to overcome the poor immune responsiveness often experienced when using self immunoglobulins as immunogens. Despite bearing a unique gene combination, and thus particular epitopes, it is normally difficult to stimulate the immune response against antibody variable regions. Different strategies are currently used to strengthen Id immunogenicity, such as concomitant use of immune-stimulating molecules, design of Id-containing immunogenic recombinant proteins, specific targeting of relevant immune cells, and genetic immunization. This review focuses on the role of anti-Id vaccination in cancer management and on the current developments used to foster anti-idiotypic B and T cell responses.

  8. Idiotypes as immunogens: facing the challenge of inducing strong therapeutic immune responses against the variable region of immunoglobulins

    Energy Technology Data Exchange (ETDEWEB)

    López-Requena, Alejandro [Molecular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Trieste (Italy); Immunobiology Division, Center of Molecular Immunology, Havana (Cuba); Bioengineering Research Institute, Biotech Pharmaceutical Co., Ltd, Beijing (China); Burrone, Oscar R.; Cesco-Gaspere, Michela, E-mail: cescogaspere@gmail.com [Molecular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Trieste (Italy)

    2012-11-09

    Idiotype (Id)-based immunotherapy has been exploited as cancer treatment option. Conceived as therapy for malignancies bearing idiotypic antigens, it has been also extended to solid tumors because of the capacity of anti-idiotypic antibodies to mimic Id-unrelated antigens. In both these two settings, efforts are being made to overcome the poor immune responsiveness often experienced when using self immunoglobulins as immunogens. Despite bearing a unique gene combination, and thus particular epitopes, it is normally difficult to stimulate the immune response against antibody variable regions. Different strategies are currently used to strengthen Id immunogenicity, such as concomitant use of immune-stimulating molecules, design of Id-containing immunogenic recombinant proteins, specific targeting of relevant immune cells, and genetic immunization. This review focuses on the role of anti-Id vaccination in cancer management and on the current developments used to foster anti-idiotypic B and T cell responses.

  9. Pathophysiology of B-cell intrinsic immunoglobulin class switch recombination deficiencies.

    Science.gov (United States)

    Durandy, Anne; Taubenheim, Nadine; Peron, Sophie; Fischer, Alain

    2007-01-01

    B-cell intrinsic immunoglobulin class switch recombination (Ig-CSR) deficiencies, previously termed hyper-IgM syndromes, are genetically determined conditions characterized by normal or elevated serum IgM levels and an absence or very low levels of IgG, IgA, and IgE. As a function of the molecular mechanism, the defective CSR is variably associated to a defect in the generation of somatic hypermutations (SHMs) in the Ig variable region. The study of Ig-CSR deficiencies contributed to a better delineation of the mechanisms underlying CSR and SHM, the major events of antigen-triggered antibody maturation. Four Ig-CSR deficiency phenotypes have been so far reported: the description of the activation-induced cytidine deaminase (AID) deficiency (Ig-CSR deficiency 1), caused by recessive mutations of AICDA gene, characterized by a defect in CSR and SHM, clearly established the role of AID in the induction of the Ig gene rearrangements underlying CSR and SHM. A CSR-specific function of AID has, however, been detected by the observation of a selective CSR defect caused by mutations affecting the C-terminus of AID. Ig-CSR deficiency 2 is the consequence of uracil-N-glycosylase (UNG) deficiency. Because UNG, a molecule of the base excision repair machinery, removes uracils from DNA and AID deaminates cytosines into uracils, that observation indicates that the AID-UNG pathway directly targets DNA of switch regions from the Ig heavy-chain locus to induce the CSR process. Ig-CSR deficiencies 3 and 4 are characterized by a selective CSR defect resulting from blocks at distinct steps of CSR. A further understanding of the CSR machinery is expected from their molecular definition.

  10. Salivary immunoglobulin classes in Nigerian smokers with periodontitis.

    Science.gov (United States)

    Olayanju, Olatunde A; Rahamon, Sheu K; Joseph, Ijeboime O; Arinola, Olatunbosun G

    2012-10-26

    To determine the levels of salivary immunoglobulin classes in Nigerian smokers and non-smokers with periodontitis. Sixty-nine individuals were recruited into this study after obtaining informed consent. They were subdivided into three groups that consisted of 20 (aged 46 ± 11 years) cigarette smokers with periodontitis (S+P); 24 (40 ± 12 years) smokers without periodontitis (S-P); and 25 (53 ± 11 years) non-smokers with periodontitis (NS+P). An oral and maxillofacial surgeon used radiographs for periodontal probing for the diagnosis of periodontitis. The smokers included subjects who smoked at least six cigarettes per day and all the periodontitis patients were newly diagnosed. About 5 mL of unstimulated saliva was expectorated by each subject into plain sample bottles. Salivary immunoglobulin levels were estimated using enzyme linked immunosorbent assay. Student's t test was used to determine significant differences between the means. Values of P vs 670.0 ± 110 ng/mL, P = 0.000) and IgM (644.5 ± 160.0 ng/mL vs 791.4 ± 43.7 ng/mL, P = 0.000) were significantly lower in the S+P compared with NS+P group. Salivary IgA (570.4 ± 145.6 ng/mL vs 670.0 ± 110 ng/mL, P = 0.008) and IgM (703.1 ± 169.3 ng/mL vs 791.4 ± 43.7 ng/mL, P = 0.012) levels were significantly lower in the S-P compared with NS+P group. Only one (5%) periodontal patient had detectable levels of salivary IgE (0.20 IU/mL). Similarly, only one smoker (4.17%) had detectable levels of salivary IgE (0.04 IU/mL) and two non-smokers (9.52%) had detectable levels of IgE (0.24 IU/mL). Our study suggests that reduced salivary IgA and IgM levels in smokers with periodontitis could enhance increased susceptibility to periodontitis.

  11. Intravenous immunoglobulin response in treatment-naïve chronic inflammatory demyelinating polyradiculoneuropathy

    NARCIS (Netherlands)

    Kuitwaard, Krista; Hahn, Angelika F.; Vermeulen, Marinus; Venance, Shannon L.; van Doorn, Pieter A.

    2015-01-01

    There is no consensus on which treatment should be used preferentially in individual patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Patients unlikely to respond to intravenous immunoglobulin (IVIg) could be prescribed corticosteroids first to avoid high cost and a delayed

  12. Solid-phase radioimmunoassay of immunoglobulins G, A and M: applicability in analysis of sucrose gradients

    Energy Technology Data Exchange (ETDEWEB)

    Eriksen, E F; Danielsen, H [Aarhus Kommunehospital (Denmark). Medical Department C; Johansen, A S [Aarhus Univ. (Denmark). Institute of Medical Biochemistry; Larsson, L I [Unit of Histochemistry, University Institute of Pathology, Copenhagen, Denmark

    1984-01-01

    A simple and sensitive solid-phase radioimmunoassay for the detection of immunoglobulins G, A and M in sucrose gradients is described. The solid-phase consisted of immunoglobulins adsorbed to polystyrene tubes. Using buffers without detergent and /sup 125/I-labeled sheep anti-rabbit IgA as radioligand, the assay was able to detect 0.8 ng per tube in the IgG assay and 1.6 ng per tube in the IgA and IgM assays. Standard curves with antigen dissolved in 10% and 32% sucrose were superimposable and did not deviate from standard curves with antigen dissolved in buffer without sucrose. Using these techniques on ultracentrifugation samples from patients with systemic lupus erythematosus, Schoenlein-Henoch nephritis and IgA glorulonephritis is was possible to detect both immunoglobulin fragments and immunoglobulin aggregates at the same time without prior dialysis of the samples.

  13. Immunoglobulins of patients with Cushing's syndrome due to pigmented adrenocortical micronodular dysplasia stimulate in vitro steroidogenesis

    NARCIS (Netherlands)

    Wulffraat, N. M.; Drexhage, H. A.; Wiersinga, W. M.; van der Gaag, R. D.; Jeucken, P.; Mol, J. A.

    1988-01-01

    The putative stimulation of adrenal steroid production by immunoglobulins (Igs) of five patients with pigmented adrenocortical micronodular dysplasia and clinical Cushing's syndrome was investigated. Ascorbate depletion, a process linked to steroid production, was measured by a cyto-chemical

  14. Salivary immunoglobulin classes in Nigerian cigarette smokers: Indication for increased risk of oral diseases

    Directory of Open Access Journals (Sweden)

    Ayodeji Olatunde Olayanju

    2012-01-01

    Conclusion: Our study showed that there is decreased salivary IgM in smokers. This observation suggests that reduced salivary immunoglobulin level of IgM might be involved in the pathogenesis of oral diseases in cigarette smokers.

  15. PARTIAL PURIFICATION AND IMMUNE-BIOCHEMICAL CHARACTERIZATION OF DOG SERUM IMMUNOGLOBULIN G

    Directory of Open Access Journals (Sweden)

    Manoj Kumar

    2013-06-01

    Full Text Available In the present study Immunoglobulin G was purified from serum of dog by gel filtration chromatography on Sephacryl S-200. SDS- PAGE analysis of purified dog IgG showed major polypeptides of 66 kDa, 52.40 kDa and 20.72 kDa. The purified Immunoglobulin has been found to be immune-reactive by DID test and Western Blot analysis when treated against hyperimmune sera which was raised in rabbit.

  16. Evaluation of salivary immunoglobulin A levels in tobacco smokers and patients with recurrent aphthous ulcers

    OpenAIRE

    Shilpashree, H. S.; Sarapur, Shriprasad

    2012-01-01

    Objectives: The aim of the present study was to analyze the influence of smoking on the salivary immunoglobulin response in smokers and to evaluate the salivary immunoglobulin A in patients with recurrent aphthous ulcers. Materials and Methods: The study included total of 80 subjects, of whom 40 were having history of chronic smoking habit, 20 were clinically diagnosed cases of recurrent aphthous ulcer and 20 were in the control group. Sample of unstimulated saliva was collected, centrifuged ...

  17. Serum immunoglobulins E are related to menstrual cycle

    International Nuclear Information System (INIS)

    Vellutini, Mariella; Viegi, Giovanni; Parrini, Donatella; Pedreschi, Marzia; Baldacci, Sandra; Modena, Paola; Biavati, Batrizia; Simoni, Marzia; Carrozzi, Laura; Giuntini, Carlo

    1997-01-01

    During a cross sectional epidemiological survey on a general population sample, 596 fertile women underwent total serum IgE determination. They completed an interviewer-administered standardized questionnaire and were categorized according to their menstrual period. They were divided into two groups: those from days 10 to 20, who were considered to be in the periovulatory phase, and those in the other phases. IgE mean values were significantly different (p = 0.01) in the two groups: particularly, lower IgE values were found in those in periovulatory phase, after accounting for smoking habit and atopic status. By multiple regression analysis, taking into account the independent effects of menstrual period, age, smoking habit, hours of fast, skin prick test reactivity and presence of cough, significantly lower IgE values in the periovulatory phase were found. We hypothesize the possibility that a decrease of IgE concentration occurs during midcycle: a reduced immune response might facilitate the ovuli implantation. Further studies are necessary to longitudinally investigate the trend of IgE in the same women, as well as the distributions and the trends of other immunoglobulins

  18. Imaging findings of primary immunoglobulin G4-related cervical lymphadenopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kawaguchi, Masaya; Kato, Hiroki; Goshima, Satoshi; Matsuo, Masayuki [Gifu University School of Medicine, Department of Radiology, Gifu (Japan); Kito, Yusuke [Gifu University School of Medicine, Department of Pathology and Translational Research, Gifu (Japan); Mizuta, Keisuke; Aoki, Mitsuhiro [Gifu University School of Medicine, Department of Otolaryngology, Gifu (Japan); Kato, Keizo [Gifu University School of Medicine, Department of Oral and Maxillofacial Sciences, Gifu (Japan)

    2017-11-15

    The purpose of the present study was to assess imaging findings of primary immunoglobulin G4 (IgG4)-related cervical lymphadenopathy. Five consecutive patients with clinically, serologically, and histopathologically confirmed primary IgG4-related cervical lymphadenopathy without any other organ involvement were included. All patients underwent contrast-enhanced computed tomography (CT), and four underwent {sup 18}F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT. We retrospectively reviewed the images and assessed the number, size, location, central necrosis, perinodal infiltration, penetrating vessels, and maximum standardized uptake values (SUVmax) of the enlarged cervical nodes. Thirteen enlarged cervical nodes measuring larger than 10 mm in minimum diameter were identified. The maximum and minimum diameter of enlarged nodes ranged from 1.2 to 3.2 cm (median, 1.8 cm) and from 1.0 to 1.9 cm (median, 1.2 cm), respectively. Lymphadenopathy was unilateral in all patients, and eight enlarged nodes were located at level IB (62%), one at level II (8%), three at level IV (23%), and one at level V (8%). Central necrosis was not seen in any nodes. Perinodal infiltration was seen in only one node (8%), and penetrating vessels were seen in seven nodes (54%). The median SUVmax of nine nodes was 4.45 (range, 2.08-12.44). Eight enlarged nodes (62%) were located in the submandibular region. Central necrosis was not observed in any nodes and perinodal infiltration was observed in one node (8%). (orig.)

  19. Clinical outcomes of intravenous immunoglobulin therapy in refractory uveitis.

    Science.gov (United States)

    Garcia-Geremias, M; Carreño, E; Epps, S J; Lee, R W J; Dick, A D

    2015-04-01

    Intravenous immunoglobulin (IVIg) therapy has multiple mechanisms of immunomodulatory action. We wished therefore to assess its efficacy in a spectrum of patients with refractory uveitis. Retrospective review of clinical charts was conducted to document response to IVIg treatment in consecutive patients with treatment-refractory uveitis. Main outcome measures were control of intraocular inflammation, visual acuity, progression of the disease, and complications. Four (two male) patients, with a mean age at the beginning of the treatment of 47 years (range: 39-64), were included in the study. Indication for treatment was patients with active non-infectious uveitis refractory to steroids and immunomodulatory therapy. All patients received a course of 0.5 g/kg per day of IVIg for three consecutive days, repeating this course at a mean of 11 week (range: 2-39 weeks) intervals when indicated clinically. The median duration of the IVIg therapy was 7 months (range: 3-14 months). In three patients treatment resulted in stabilisation and prevention of progression of the disease, and additionally in two patients it facilitated a decrease in prednisolone dose. Treatment failed to induce long-term remission in one patient with recurrence of macular oedema. IVIg was well tolerated with neither immediate nor longer-term adverse events observed. In three out of four cases IVIg was an effective adjunctive therapy and well tolerated for the management of treatment-refractory uveitis.

  20. Intravenous Immunoglobulin Protects Against Severe Pandemic Influenza Infection

    Directory of Open Access Journals (Sweden)

    Steven Rockman

    2017-05-01

    Full Text Available Influenza is a highly contagious, acute, febrile respiratory infection that can have fatal consequences particularly in individuals with chronic illnesses. Sporadic reports suggest that intravenous immunoglobulin (IVIg may be efficacious in the influenza setting. We investigated the potential of human IVIg to ameliorate influenza infection in ferrets exposed to either the pandemic H1N1/09 virus (pH1N1 or highly pathogenic avian influenza (H5N1. IVIg administered at the time of influenza virus exposure led to a significant reduction in lung viral load following pH1N1 challenge. In the lethal H5N1 model, the majority of animals given IVIg survived challenge in a dose dependent manner. Protection was also afforded by purified F(ab′2 but not Fc fragments derived from IVIg, supporting a specific antibody-mediated mechanism of protection. We conclude that pre-pandemic IVIg can modulate serious influenza infection-associated mortality and morbidity. IVIg could be useful prophylactically in the event of a pandemic to protect vulnerable population groups and in the critical care setting as a first stage intervention.

  1. Natural immunoglobulins (contribution to a debate on biomedical education

    Directory of Open Access Journals (Sweden)

    Vaz Nelson M

    2000-01-01

    Full Text Available Immunology has contributed to biomedical education in many important ways since the creation of scientific medicine in the last quarter of the 19th century. Today, immunology is a major area of biomedical research. Nevertheless, there are many basic problems unresolved in immunological activities and phenomena. Solving these problems is probably necessary to devise predictable and safe ways to produce new vaccines, treat allergy and autoimmune diseases and perform safe transplants. This challenge involves not only technical developments but also changes in attitude, of which the most fundamental is to abandon the traditional stimulus-response perspective in favor of more "systemic" views. Describing immunological activities as the operation of a complex multiconnected network, raises biological and epistemological issues not usually dealt with in biomedical education. Here we point to one example of systemic approaches. A new form of immunoblot (Panama blot, by which the reaction of natural immunoglobulins with complex protein mixtures may be analyzed by a special software and multivariate statistics, has been recently used to characterize human autoimmune diseases. Our preliminary data show that Panama blots can also be used to characterize global (systemic immunogical changes in chronic human parasitic diseases, such as malaria and schistosomiasis mansoni, that correlate with the clinical status.

  2. [Batch release of immunoglobulin and monoclonal antibody products].

    Science.gov (United States)

    Gross, S

    2014-10-01

    The Paul-Ehrlich Institute (PEI) is an independent institution of the Federal Republic of Germany responsible for performing official experimental batch testing of sera. The institute decides about the release of each batch and performs experimental research in the field. The experimental quality control ensures the potency of the product and also the absence of harmful impurities. For release of an immunoglobulin batch the marketing authorization holder has to submit the documentation of the manufacture and the results of quality control measures together with samples of the batch to the PEI. Experimental testing is performed according to the approved specifications regarding the efficacy and safety. Since implementation of the 15th German drug law amendment, the source of antibody is not defined anymore. According to § 32 German drug law, all batches of sera need to be released by an official control laboratory. Sera are medicinal products, which contain antibodies, antibody fragments or fusion proteins with a functional antibody portion. Therefore, all batches of monoclonal antibodies and derivatives must also be released by the PEI and the marketing authorization holder has to submit a batch release application. Under certain circumstances a waiver for certain products can be issued with regard to batch release. The conditions for such a waiver apply to the majority of monoclonal antibodies.

  3. Effect of radioiodine on stimulatory activity of Graves' immunoglobulins

    International Nuclear Information System (INIS)

    Atkinson, S.; McGregor, A.M.; Kendall-Taylor, P.; Peterson, M.M.; Smith, B.R.

    1982-01-01

    The effects of 131 I therapy on the activity of thyroid stimulating antibody (TSAb) and thyrotrophin binding inhibiting immunoglobulin (TBII) in nineteen patients with Graves' disease have been studied. Prior to 131 I administration, TSAb was detected in 84%, and TBII in 68% of patients. Following 131 I administration TSAb and TBII were detectable in 100% of patients. The elevation 3 months after treatment of the means of both the TSAb and TBII indices for the group of nineteen patients was highly significant compared with pretreatment values. All the patients went into remission during the course of the study and the TSAb index declined in all patients, becoming undetectable in eleven; TBII also declined in most patients but remained detectable in thirteen. The study furthermore afforded the opportunity for a direct comparison of binding with stimulatory activity. These results show that after 131 I therapy for Graves' hyperthyroidism there is a transient increase in TSAb as well as TBII, followed by a decline, and that the measurement of binding and stimulatory activities are in good general agreement. (author)

  4. Glycosylation of immunoglobulin A influences its receptor binding.

    Science.gov (United States)

    Basset, C; Devauchelle, V; Durand, V; Jamin, C; Pennec, Y L; Youinou, P; Dueymes, M

    1999-12-01

    Immunoglobulin A (IgA), which is heavily glycosylated, interacts with a variety of receptors, e.g. the asialoglycoprotein receptor (ASGP-R), which binds terminal galactose residues, and the Fcalpha receptor (FcalphaRI). It has thus been proposed that elevated serum levels of IgA in primary Sjögren's syndrome (pSS) are caused by its defective clearance. To test this hypothesis, we developed a method (based on sialyl transferases eluted from a hepatoma cell line) to increase the amount of sialic acid (SA) on IgA, and used a battery of IgA1- and IgA2-specific glycosidases to reduce this amount. Binding of IgA1 and IgA2 to ASGP-R and FcalphaRI was found to be sugar dependent because oversialylated IgA bound less than native or desialylated IgA. However, individual sugars did not play a direct role in this binding. Given that IgA are oversialylated in pSS, defective clearance of IgA may indeed be ascribed to an excess of SA in IgA1 and IgA2.

  5. Imaging findings of primary immunoglobulin G4-related cervical lymphadenopathy

    International Nuclear Information System (INIS)

    Kawaguchi, Masaya; Kato, Hiroki; Goshima, Satoshi; Matsuo, Masayuki; Kito, Yusuke; Mizuta, Keisuke; Aoki, Mitsuhiro; Kato, Keizo

    2017-01-01

    The purpose of the present study was to assess imaging findings of primary immunoglobulin G4 (IgG4)-related cervical lymphadenopathy. Five consecutive patients with clinically, serologically, and histopathologically confirmed primary IgG4-related cervical lymphadenopathy without any other organ involvement were included. All patients underwent contrast-enhanced computed tomography (CT), and four underwent 18 F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT. We retrospectively reviewed the images and assessed the number, size, location, central necrosis, perinodal infiltration, penetrating vessels, and maximum standardized uptake values (SUVmax) of the enlarged cervical nodes. Thirteen enlarged cervical nodes measuring larger than 10 mm in minimum diameter were identified. The maximum and minimum diameter of enlarged nodes ranged from 1.2 to 3.2 cm (median, 1.8 cm) and from 1.0 to 1.9 cm (median, 1.2 cm), respectively. Lymphadenopathy was unilateral in all patients, and eight enlarged nodes were located at level IB (62%), one at level II (8%), three at level IV (23%), and one at level V (8%). Central necrosis was not seen in any nodes. Perinodal infiltration was seen in only one node (8%), and penetrating vessels were seen in seven nodes (54%). The median SUVmax of nine nodes was 4.45 (range, 2.08-12.44). Eight enlarged nodes (62%) were located in the submandibular region. Central necrosis was not observed in any nodes and perinodal infiltration was observed in one node (8%). (orig.)

  6. [Identification and production of monoclonal antibody of Siberian tiger's immunoglobulin].

    Science.gov (United States)

    Zhang, Yaonglong; Zhang, Duanling; Zhou, Ming; Xue, Yuan; Hua, Yuping; Ma, Jianzhang

    2010-03-01

    To purify immunoglobulin (Ig) of Siberian Tiger and prepare monoclonal antibody (mAb) against the Ig,which can be used to develop immunological diagnostic kits for diagnosing infectious disease in Siberian Tiger. The Ig of Siberian tigers was purified with saturated ammonium sulfate combined with recombinant Protein G. The C57BL/6 mice were immunized with the purified Ig. Spleno-cytes of the mice immunized were collected and fused with the mouse myeloma cell line (Sp2/0-Ag14). The positive hybridoma clones were selected by ELISA and were identified by western blot. The sandwich ELISA was used to detect immunocompetence of the purified Ig and the mAb. We obtained three mouse hybridoma clones that produced mAbs against Ig of Siberian Tiger. The derived McAbs could recognize Ig heavy chain of Siberian Tiger specifically. The biological activity of the Ig and obtained McAbs also could be identified by detecting the antibody induced by panleukopenia virus (FPV-HLJ) vaccine in Siberian Tiger. The antibody also would be useful for assess the vaccine efficacy against the infectious disease on the Siberian Tiger. Protein G can be used in Ig purification of Siberian Tiger. The obtained McAbs from the hybridoma ADT11 in this study owned strong ability to bind Ig of Siberian Tiger and have a stable immunocompetence. They can be used to develop diagnostic methods for detecting infectious disease in Siberian Tiger and vaccine research.

  7. Gut microbiota utilize immunoglobulin A for mucosal colonization.

    Science.gov (United States)

    Donaldson, G P; Ladinsky, M S; Yu, K B; Sanders, J G; Yoo, B B; Chou, W-C; Conner, M E; Earl, A M; Knight, R; Bjorkman, P J; Mazmanian, S K

    2018-05-18

    The immune system responds vigorously to microbial infection while permitting lifelong colonization by the microbiome. Mechanisms that facilitate the establishment and stability of the gut microbiota remain poorly described. We found that a regulatory system in the prominent human commensal Bacteroides fragilis modulates its surface architecture to invite binding of immunoglobulin A (IgA) in mice. Specific immune recognition facilitated bacterial adherence to cultured intestinal epithelial cells and intimate association with the gut mucosal surface in vivo. The IgA response was required for B. fragilis (and other commensal species) to occupy a defined mucosal niche that mediates stable colonization of the gut through exclusion of exogenous competitors. Therefore, in addition to its role in pathogen clearance, we propose that IgA responses can be co-opted by the microbiome to engender robust host-microbial symbiosis. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  8. Chemical stabilization of porous silicon for enhanced biofunctionalization with immunoglobulin

    Directory of Open Access Journals (Sweden)

    Nelson Naveas, Vicente Torres Costa, Dario Gallach, Jacobo Hernandez-Montelongo, Raul Jose Martín Palma, Josefa Predenstinacion Garcia-Ruiz and Miguel Manso-Silván

    2012-01-01

    Full Text Available Porous silicon (PSi is widely used in biological experiments, owing to its biocompatibility and well-established fabrication methods that allow tailoring its surface. Nevertheless, there are some unresolved issues such as deciding whether the stabilization of PSi is necessary for its biological applications and evaluating the effects of PSi stabilization on the surface biofunctionalization with proteins. In this work we demonstrate that non-stabilized PSi is prone to detachment owing to the stress induced upon biomolecular adsorption. Biofunctionalized non-stabilized PSi loses the interference properties characteristic of a thin film, and groove-like structures resulting from a final layer collapse were observed by scanning electron microscopy. Likewise, direct PSi derivatization with 3-aminopropyl-triethoxysilane (APTS does not stabilize PSi against immunoglobulin biofunctionalization. To overcome this problem, we developed a simple chemical process of stabilizing PSi (CoxPSi for biological applications, which has several advantages over thermal stabilization (ToxPSi. The process consists of chemical oxidation in H2O2, surface derivatization with APTS and a curing step at 120 °C. This process offers integral homogeneous PSi morphology, hydrophilic surface termination (contact angle θ = 26° and highly efficient derivatized and biofunctionalized PSi surfaces (six times more efficient than ToxPSi. All these features are highly desirable for biological applications, such as biosensing, where our results can be used for the design and optimization of the biomolecular immobilization cascade on PSi surfaces.

  9. Importance of neonatal immunoglobulin transfer for hippocampal development and behaviour in the newborn pig.

    Directory of Open Access Journals (Sweden)

    Kateryna Goncharova

    Full Text Available Neurological disorders are among the main clinical problems affecting preterm children and often result in the development of communication and learning disabilities later in life. Several factors are of importance for brain development, however the role of immunoglobulins (passive immunity transfer has not yet been investigated. Piglets are born agammaglobulinemic, as a result of the lack of transfer of maternal immunoglobulins in utero, thus, they serve as an ideal model to mimic the condition of immunoglobulin deficiency in preterm infants. Thirty six, unsuckled newborn piglets were fed an infant formula or colostrum and supplemented orally or intravenously with either species-specific or foreign immunoglobulin and then compared to both newborn and sow-reared piglets. Two days after the piglets were born behavioural tests (novel recognition and olfactory discrimination of conspecifics scent were performed, after which the piglets were sacrificed and blood, cerebrospinal fluid and hippocampi samples were collected for analyses. Both parameters of neuronal plasticity (neuronal maturation and synapse-associated proteins and behavioural test parameters appeared to be improved by the appearance of species-specific porcine immunoglulin in the circulation and cerebrospinal fluid of the piglets. In conclusion, we postulate possible positive clinical effects following intravenous infusion of human immunoglobulin in terms of neuronal plasticity and cognitive function in preterm infants born with low blood immunoglobulin levels.

  10. Optimized localization of bacterial infections with technetium-99m labelled human immunoglobulin after protein charge selection

    International Nuclear Information System (INIS)

    Welling, M.; Feitsma, H.I.J.; Calame, W.; Ensing, G.J.; Goedemans, W.; Pauwels, E.K.J.

    1994-01-01

    To improve the scintigraphic detection of bacterial infections a protein charge-purified fraction of polyclonal human immunoglobulin was applied as a radiopharmaceutical. This purification was achieved by attaching the immunoglobulin to an anion-exchanger column and by obtaining the column-bound fraction with buffer. The binding to bacteria in vitro and the target to non-target ratios of an experimental thigh infection with Staphylococcus aureus or Klebsiella pneumoniae in mice were evaluated to compare the purified and the unpurified immunoglobulin. The percentage of binding to all gram-positive and gram-negative bacteria used in this study was significantly (P 99m Tc-labelled protein charge-purified polyclonal human immunoglobulin was administered intravenously. At all time intervals the target (infected thighs) to non-target (non-infected thighs) ratios for both infections were significantly higher (P 99m Tc-labelled protein charge-purified immunoglobulin localizes both a gram-positive and a gram-negative thigh infection more intensely and faster than 99m Tc-labelled unpurified immunoglobulin. (orig.)

  11. Monoclonal antibodies to snakehead, Channa striata immunoglobulins: detection and quantification of immunoglobulin-positive cells in blood and lymphoid organs.

    Science.gov (United States)

    Sood, Neeraj; Chaudhary, Dharmendra K; Rathore, Gaurav; Singh, Akhilesh; Lakra, W S

    2011-02-01

    Snakehead Channa striata is an important freshwater food fish in many Southeast Asian countries. Three monoclonal antibodies (C9, C10 and D10) were developed against purified serum immunoglobulins of Channa striata (Cs-Ig) and characterized. C9 and D10 MAbs were specific to heavy chain, while C10 MAb detected only unreduced Cs-Ig in western blotting. In competitive ELISA, C9 and C10 MAbs were specific to C. striata Ig and showed no cross reactivity with serum Ig of other fish species i.e. Channa punctatus, Channa marulius, Clarias batrachus and Labeo rohita. D10 MAb showed reactivity to serum Ig of C. striata and C. marulius. In FACS analysis of gated lymphocytes, the percentage of Ig+ cells detected by C9 MAb was 18.2%, 27.7% and 10.3% in blood, spleen and kidney, respectively (n=3, body weight 500-600 g). However, only a few cells (0.5%) were found to be Ig+ in thymus (n=5). C9 MAb was also successfully employed to demonstrate Ig+ cells in blood smears and formalin fixed sections of spleen and kidney. These findings suggest that the spleen plays an important role in humoral immunity as compared to head kidney. Further, these MAbs can be useful immunological tool in monitoring health status of cultured C. striata. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Immunoparesis and polyclonal immunoglobulin recovery after auto-SCT for patients with multiple myeloma treated at a single institution.

    Science.gov (United States)

    Jimenez-Zepeda, Victor H; Duggan, Peter; Neri, Paola; Chaudhry, Ahsan; Tay, Jason; Bahlis, Nizar

    2017-11-21

    Immunoparesis and polyclonal immunoglobulin recovery have been recently described as common indicators of immune dysfunction in patients with multiple myeloma. In the present study, we aimed to assess the impact of immunoparesis and polyclonal immunoglobulin recovery at day-100 post autologous stem cell transplant (auto-SCT) on clinical outcomes. A total of 302 patients were included for the analysis of immunoparesis, and 197 were evaluable for polyclonal immunoglobulin recovery evaluation. Immunoparesis was observed in 93.5% of cases, with 47% of cases having polyclonal immunoglobulin recovery at 12 months post auto-SCT. Median overall and progression-free survival were longer in the group of patients with complete or partial normalization of polyclonal immunoglobulins. Patients receiving consolidation had a lower level of polyclonal reconstitution. In conclusion, polyclonal immunoglobulin recovery by 12 months post-auto-SCT is associated with superior overall and progression free survival in patients with MM. Efforts to better enhance polyclonal recovery deserve further investigation.

  13. Tattooing to "Toughen up": Tattoo experience and secretory immunoglobulin A.

    Science.gov (United States)

    Lynn, Christopher D; Dominguez, Johnna T; DeCaro, Jason A

    2016-09-10

    A costly signaling model suggests tattooing inoculates the immune system to heightened vigilance against stressors associated with soft tissue damage. We sought to investigate this "inoculation hypothesis" of tattooing as a costly honest signal of fitness. We hypothesized that the immune system habituates to the tattooing stressor in repeatedly tattooed individuals and that immune response to the stress of the tattooing process would correlate with lifetime tattoo experience. Participants were 24 women and 5 men (aged 18-47). We measured immune function using secretory immunoglobulin A (SIgA) and cortisol (sCORT) in saliva collected before and after tattoo sessions. We measured tattoo experience as a sum of number of tattoos, lifetime hours tattooed, years since first tattoo, percent of body covered, and number of tattoo sessions. We predicted an inverse relationship between SIgA and sCORT and less SIgA immunosuppression among those with more tattoo experience. We used hierarchical multiple regression to test for a main effect of tattoo experience on post-tattoo SIgA, controlling for pretest SIgA, tattoo session duration, body mass, and the interaction between tattoo experience and test session duration. The regression model was significant (P = 0.006) with a large effect size (r(2)  = 0.711) and significant and positive main (P = 0.03) and interaction effects (P = 0.014). Our data suggest that the body habituates over time to the tattooing stressor. It is possible that individuals with healthy immune systems heal faster, making them more likely to get multiple tattoos. Am. J. Hum. Biol. 28:603-609, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Exquisite response to intravenous immunoglobulin in Susac syndrome during pregnancy

    Directory of Open Access Journals (Sweden)

    Enrique Gomez-Figueroa

    2018-03-01

    Full Text Available Introduction: From its initial report on two female patients in 1979 by J.O. Susac, Susac syndrome (SuS or SICRET (small infarctions of cochlear, retinal and encephalic tissue has persisted as an elusive entity. To date the available evidence for its treatment is based on case reports and case series. The largest systematic review described only 304 reported cases since the 1970s. Here we presented the first reported case to our knowledge in Mexican population and the unusual presentation in a pregnant patient. Case presentation: A 34-year-old Hispanic woman was brought to the ER in our hospital for apathy and behavioral changes. Upon arrival at the ER, her husband described a one-month history of behavioral changes with apathy, progressive abulia, visuospatial disorientation, and gait deterioration. The initial lab test shows no significance except by a positive qualitative hCG. An MRI was obtained and showed hyperintense periventricular white matter lesions in T2 and FLAIR sequences also involving bilateral basal ganglia and with predominant affection of the corpus callosum, in addition to infratentorial cerebellar lesions. After treatment with intravenous immunoglobulins a marked and prompt clinical and radiological improvement was observed. Conclusion: SuS is still an elusive disease. To date, no definitive score or clinical feature can predict the outcome of the disease. The presentation during pregnancy is also rare and therefore the optimal treatment and the prognosis is unknown. We hope that this article will serve as a foundation for future research. Keywords: Susac syndrome, Neuroinflammation, Corpus callosum, Demyelinating disease, Vasculitis

  15. SCM, the M Protein of Streptococcus canis Binds Immunoglobulin G.

    Science.gov (United States)

    Bergmann, Simone; Eichhorn, Inga; Kohler, Thomas P; Hammerschmidt, Sven; Goldmann, Oliver; Rohde, Manfred; Fulde, Marcus

    2017-01-01

    The M protein of Streptococcus canis (SCM) is a virulence factor and serves as a surface-associated receptor with a particular affinity for mini-plasminogen, a cleavage product of the broad-spectrum serine protease plasmin. Here, we report that SCM has an additional high-affinity immunoglobulin G (IgG) binding activity. The ability of a particular S. canis isolate to bind to IgG significantly correlates with a scm -positive phenotype, suggesting a dominant role of SCM as an IgG receptor. Subsequent heterologous expression of SCM in non-IgG binding S. gordonii and Western Blot analysis with purified recombinant SCM proteins confirmed its IgG receptor function. As expected for a zoonotic agent, the SCM-IgG interaction is species-unspecific, with a particular affinity of SCM for IgGs derived from human, cats, dogs, horses, mice, and rabbits, but not from cows and goats. Similar to other streptococcal IgG-binding proteins, the interaction between SCM and IgG occurs via the conserved Fc domain and is, therefore, non-opsonic. Interestingly, the interaction between SCM and IgG-Fc on the bacterial surface specifically prevents opsonization by C1q, which might constitute another anti-phagocytic mechanism of SCM. Extensive binding analyses with a variety of different truncated SCM fragments defined a region of 52 amino acids located in the central part of the mature SCM protein which is important for IgG binding. This binding region is highly conserved among SCM proteins derived from different S. canis isolates but differs significantly from IgG-Fc receptors of S. pyogenes and S. dysgalactiae sub. equisimilis , respectively. In summary, we present an additional role of SCM in the pathogen-host interaction of S. canis . The detailed analysis of the SCM-IgG interaction should contribute to a better understanding of the complex roles of M proteins in streptococcal pathogenesis.

  16. Predictors of nonresponse to intravenous immunoglobulin therapy in Kawasaki disease

    Directory of Open Access Journals (Sweden)

    Hyo Min Park

    2013-02-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; It has been reported that 10% to 20% of children with Kawasaki disease (KD will not respond to intravenous immunoglobulin (IVIG treatment. In this study, we aimed to identify useful predictors of therapeutic failure in children with KD. &lt;b&gt;Methods:&lt;/b&gt; We examined 309 children diagnosed with KD at the Kyungpook National University Hospital and the Inje University Busan Paik Hospital between January 2005 and June 2011. We retrospectively reviewed their medical records and analyzed multiple parameters in responders and nonresponders to IVIG. &lt;b&gt;Results:&lt;/b&gt; Among the 309 children, 30 (9.7% did not respond to IVIG. They had significantly higher proportion of neutrophils, and higher levels of aspartate aminotransferase, alanine aminotransferase (ALT, total bilirubin, and N-terminal fragment of B-type natriuretic peptide than did responders. IVIGnonresponders had a significantly longer duration of hospitalization, and more frequently experienced coronary artery lesion, and sterile pyuria. No differences in the duration of fever at initial treatment or, clinical features were noted. &lt;b&gt;Conclusion:&lt;/b&gt; Two independent predictors (ALT?#248;4 IU/L, total bilirubin?#240;.9 mg/dL for nonresponse were confirmed through multivariate logistic regression analysis. Thus elevated ALT and total bilirubin levels might be useful in predicting nonresponse to IVIG therapy in children with KD.

  17. A phase 3 trial of IV immunoglobulin for Alzheimer disease.

    Science.gov (United States)

    Relkin, Norman R; Thomas, Ronald G; Rissman, Robert A; Brewer, James B; Rafii, Michael S; van Dyck, Christopher H; Jack, Clifford R; Sano, Mary; Knopman, David S; Raman, Rema; Szabo, Paul; Gelmont, David M; Fritsch, Sandor; Aisen, Paul S

    2017-05-02

    We tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia. In a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 months on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale; the primary functional outcome was 18-month change on the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. Safety and tolerability data, as well as serial MRIs and plasma samples, were collected throughout the study from all enrolled participants. No beneficial effects were observed in the dual primary outcome measures for the 2 IVIg doses tested. Significant decreases in plasma Aβ42 (but not Aβ40) levels were observed in IVIg-treated participants. Analysis of safety data showed no difference between IVIg and placebo in terms of the rate of occurrence of amyloid-related imaging abnormalities (brain edema or microhemorrhage). IVIg-treated participants had more systemic reactions (chills, rashes) but fewer respiratory infections than participants receiving placebo. Participants with mild to moderate AD showed good tolerability of treatment with low-dose human IVIg for 18 months but did not show beneficial effects on cognition or function relative to participants who received placebo. NCT00818662. This study provides Class II evidence that IVIg infusions performed every 2 weeks do not improve cognition or function at 18 months in patients with mild to moderate AD. © 2017 American Academy of Neurology.

  18. Intravenous immunoglobulin to treat hyperbilirubinemia in neonates with isolated Glucose-6-Phosphate dehydrogenase deficiency

    Directory of Open Access Journals (Sweden)

    Wadah Khriesat

    2017-04-01

    Full Text Available Background Glucose-6-phosphate dehydrogenase deficiency alone or concomitant with ABO isoimmunisation is a widespread indication for neonatal exchange transfusion. Aims To evaluate the effectiveness of Intravenous Immunoglobulin in the treatment of neonatal hyperbilirubinemia due to glucose-6-phosphate dehydrogenase deficiency. Methods A retrospective cohort study was conducted between 2006 and 2014 at the Jordan University of Science and technology. The medical records of 43 infants admitted to the neonatal intensive care unit for isolated glucose-6- phosphate dehydrogenase deficiency hemolytic disease of the newborns were reviewed. Patients were divided into two groups. Group I, a historical cohort, included newborns born between 2006 and 2010, Treatment included phototherapy and exchange transfusion. Group II included newborns born between 2011 and 2014, where, in addition to phototherapy, intravenous immunoglobulin was administered. The duration of phototherapy and number of exchange transfusions were evaluated. Results Of 412 newborns that were admitted with neonatal hyperbilirubinemia, Glucose-6-phosphate dehydrogenase deficiency was present in 43. Of these, 22, did not receive intravenous immunoglobulin and served as a control group. The other 21 newborns received intravenous immunoglobulin. There was no difference in the demographic characteristics between the two groups. Infants in the control group were significantly more likely to receive exchange blood transfusion than infants in the immunoglobulin treatment group, but were significantly less likely to need phototherapy. Conclusion Intravenous immunoglobulin is an effective alternative to exchange transfusion in infants with glucose-6-phosphate dehydrogenase deficiency hemolytic disease of the newborn. It is suggested that intravenous immunoglobulin may be beneficial as a prophylaxis for infants with hyperbilirubinemia.

  19. Significant differences in physicochemical properties of human immunoglobulin kappa and lambda CDR3 regions

    Directory of Open Access Journals (Sweden)

    Catherine L Townsend

    2016-09-01

    Full Text Available Antibody variable regions are composed of a heavy and a light chain and in humans there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain CDR-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 - light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains, and probed the Protein Data Bank (PDB to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda and heavy chain gene rearrangements are correlated within donors, but can differ between donors. This indicates that TdT may work with differing efficiencies between different people, but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

  20. Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions.

    Science.gov (United States)

    Townsend, Catherine L; Laffy, Julie M J; Wu, Yu-Chang Bryan; Silva O'Hare, Joselli; Martin, Victoria; Kipling, David; Fraternali, Franca; Dunn-Walters, Deborah K

    2016-01-01

    Antibody variable regions are composed of a heavy and a light chain, and in humans, there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain complementarity-determining region (CDR)-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains and probed the Protein Data Bank to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda, and heavy chain gene rearrangements are correlated within donors but can differ between donors. This indicates that terminal deoxynucleotidyl transferase may work with differing efficiencies between different people but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

  1. Uptake and intra-inclusion accumulation of exogenous immunoglobulin by Chlamydia-infected cells

    Directory of Open Access Journals (Sweden)

    Croteau Nancy L

    2008-12-01

    Full Text Available Abstract Background Obligate intracellular pathogens belonging to the Chlamydiaceae family possess a number of mechanisms by which to manipulate the host cell and surrounding environment. Such capabilities include the inhibition of apoptosis, down-regulation of major histocompatability complex (MHC and CD1/d gene expression, and the acquisition of host-synthesized nutrients. It is also documented that a limited number of host-derived macromolecules such as β-catenin and sphingomyelin accumulate within the inclusion. Results This report provides evidence that immunoglobulin, inherently present in the extracellular environment in vivo and in vitro, enters infected cells and accumulates within the chlamydial inclusion. Using epi-fluorescent and confocal microscopy, this selective uptake of Ig is shown to occur among human leukocytes in vivo as well as cells cultured in vitro. These findings were confirmed by detection of IgG in the lysate of infected cells by western blot hybridization. Sequestered antibodies appear to be present during the entire course of the chlamydial developmental cycle and are distributed throughout this compartment. IgG pre-labeled with fluorescein, when added to the supernatant of infected cell cultures, was also imported and readily visualized. Accumulation of these molecules within the inclusion and the failure of bovine serum albumin or F(ab'2 fragments to accumulate in a similar manner suggests the process of entry is specific for intact IgG molecules and not a result of pinocytosis, diffusion, or any other mass endocytic event. Conclusion Sequestration of a host cell-derived protein within the chlamydial inclusion, although unexpected, is not an unprecedented occurrence. However, selective accumulation of an exogenous host protein, such as extracellular IgG, has not been previously reported in connection with chlamydial infections. The selectivity of this process may indicate that this uptake plays an important role

  2. Immunoglobulin lambda light chain gene rearrangements in human B-cell malignancies

    NARCIS (Netherlands)

    T. Tümkaya (Talip)

    1997-01-01

    textabstractLymphocytes form the specific immune system, capable of recognizing and responding to any foreign antigen, while remaining indifferent to self components. Throughout human life, lymphocytes are continuously generated from pluripotent hematopoietic stem cells. These hematopoietic stem

  3. Altering the spectrum of immunoglobulin V gene somatic hypermutation by modifying the active site of AID.

    Science.gov (United States)

    Wang, Meng; Rada, Cristina; Neuberger, Michael S

    2010-01-18

    High-affinity antibodies are generated by somatic hypermutation with nucleotide substitutions introduced into the IgV in a semirandom fashion, but with intrinsic mutational hotspots strategically located to optimize antibody affinity maturation. The process is dependent on activation-induced deaminase (AID), an enzyme that can deaminate deoxycytidine in DNA in vitro, where its activity is sensitive to the identity of the 5'-flanking nucleotide. As a critical test of whether such DNA deamination activity underpins antibody diversification and to gain insight into the extent to which the antibody mutation spectrum is dependent on the intrinsic substrate specificity of AID, we investigated whether it is possible to change the IgV mutation spectrum by altering AID's active site such that it prefers a pyrimidine (rather than a purine) flanking the targeted deoxycytidine. Consistent with the DNA deamination mechanism, B cells expressing the modified AID proteins yield altered IgV mutation spectra (exhibiting a purine-->pyrimidine shift in flanking nucleotide preference) and altered hotspots. However, AID-catalyzed deamination of IgV targets in vitro does not yield the same degree of hotspot dominance to that observed in vivo, indicating the importance of features beyond AID's active site and DNA local sequence environment in determining in vivo hotspot dominance.

  4. Altering the spectrum of immunoglobulin V gene somatic hypermutation by modifying the active site of AID

    OpenAIRE

    Wang, Meng; Rada, Cristina; Neuberger, Michael S.

    2010-01-01

    High-affinity antibodies are generated by somatic hypermutation with nucleotide substitutions introduced into the IgV in a semirandom fashion, but with intrinsic mutational hotspots strategically located to optimize antibody affinity maturation. The process is dependent on activation-induced deaminase (AID), an enzyme that can deaminate deoxycytidine in DNA in vitro, where its activity is sensitive to the identity of the 5?-flanking nucleotide. As a critical test of whether such DNA deaminati...

  5. Genetic Diversity of the Leptospiral Immunoglobulin-like (Lig) Genes in Pathogenic Leptospira spp.

    Science.gov (United States)

    Recent serologic, immunoprotection, and pathogenesis studies implicate the Lig proteins as key virulence determinants in interactions of leptospiral pathogens with the mammalian host. We examined the sequence variation and recombination patterns of ligA, ligB, and ligC among 10 pathogenic strains. M...

  6. METHODOLOGICAL APPROACHES TO EXPERT EVALUATION OF PRECLINICAL AND CLINICAL TRIALS OF HUMAN IMMUNOGLOBULIN PRODUCTS

    Directory of Open Access Journals (Sweden)

    V. B. Ivanov

    2017-01-01

    Full Text Available The article considers the experience of Russian and leading foreign regulatory agencies in organisation and conduction of preclinical and clinical trials of human immunoglobulin products. The authors suggest a classification of human immunoglobulins and provide updated information on authorization of these products in Russia. The article summarizes methodological approaches, basic scientific principles and criteria relating to expert evaluation of preclinical and clinical trials of blood products. The authors further define the expert body’s requirements for data on preclinical and clinical trials of human normal immuniglobulins and human specific immunoglobulins for the prevention and/or treatment of infectious and non-infectious diseases which are submitted as part of applications for marketing authorization or marketing authorization variation. The article suggests programs of preclinical and clinical trials for human normal immunoglobulins and human specific immunoglobulins for the prevention and/or treatment of infectious and non-infectious diseases that are aligned with the Russian legislation and Eurasian Economic Union’s regulations on medicines circulation, and have been elaborated with respect to the guidelines of the European Medicines Agency.

  7. Dynamics of anti-VAR2CSA immunoglobulin G response in a cohort of senegalese pregnant women

    DEFF Research Database (Denmark)

    Tuikue Ndam, N G; Salanti, A; Le-Hesran, J-Y

    2006-01-01

    demonstrated that a single P. falciparum infection was able to trigger a VAR2CSA-specific antibody response. Among women with infected placentas, women with high anti-VAR2CSA IgG levels at enrollment were more likely to present with a past infection than with an acute/chronic infection. CONCLUSIONS: Anti-VAR2...... (VSAPAM). Several studies have shown that 1 var gene, var2csa, is transcribed at high levels and expressed in CSA-binding Plasmodium falciparum parasites. METHODS: Plasma levels of anti-VAR2CSA immunoglobulin G (IgG) in Senegalese women were measured during pregnancy by enzyme-linked immunosorbent assay......, using 3 recombinant proteins representing 3 domains of the var2csa gene product. RESULTS: The 3 recombinant proteins were specifically recognized by plasma from pregnant women but not by control plasma. A parity-dependent recognition pattern was observed with 2 of the 3 VAR2CSA antigens. A kinetic study...

  8. Expression of immunoglobulin G in human podocytes, and its role in cell viability and adhesion.

    Science.gov (United States)

    Jing, Ziyang; Deng, Hui; Ma, Junfan; Guo, Yanhong; Liang, Yaoxian; Wu, Rui; A, Lata; Geng, Zihan; Qiu, Xiaoyan; Wang, Yue

    2018-06-01

    Podocyte injury occurs during the initiation and development of numerous forms of glomerular disease, and antibodies targeting podocytes have become a biomarker for diagnosis and monitoring treatment response. Accumulating evidence has suggested that immunoglobulin (Ig) is expressed in non‑B lineage cells, including epithelial cancer cells, myeloid cells and several types of normal cells. The main aim of the present study was to ascertain the expression of IgG in human podocytes and to determine its potential role in cellular bioactivity. The present study detected positive staining for IgG heavy chain (Igγ) and its subtype γ4, and the light chains κ and λ in the cytoplasm or on the membrane by immunofluorescence. In addition, positive bands were detected for Igγ, γ1, γ3, γ4, κ and λ in the lysates of a podocyte cell line by western blotting. Mass spectrometry confirmed IgG1 as an intact tetramer in the culture supernatant. Constant region transcripts of Igγ, γ1, γ3, γ4, κ and λ were identified by reverse transcription‑polymerase chain reaction, and DNA sequencing of these transcripts revealed 96‑99% similarity with Ig mRNAs in the National Center for Biotechnology Information database. Compared with the diverse gene rearrangements from B cell-derived Ig, podocyte‑derived Ig exhibited conservative V(D)J patterns in the variable regions of Igγ and κ chains. Furthermore, the present study investigated the mechanism underlying IgG production in these cells by examining the expression of recombination activating gene (RAG)1, RAG2 and activation‑induced cytidine deaminase. The expression levels of these proteins suggested that podocyte‑derived Ig and traditional Ig may be generated in a similar manner. Furthermore, small interfering RNA‑mediated downregulation of IgG expression reduced podocyte viability and adhesive capabilities. These findings suggested that IgG is expressed in podocytes and that this expression may be associated

  9. Ku70 is required for late B cell development and immunoglobulin heavy chain class switching.

    Science.gov (United States)

    Manis, J P; Gu, Y; Lansford, R; Sonoda, E; Ferrini, R; Davidson, L; Rajewsky, K; Alt, F W

    1998-06-15

    Immunoglobulin (Ig) heavy chain (HC) class switch recombination (CSR) is a late B cell process that involves intrachromosomal DNA rearrangement. Ku70 and Ku80 form a DNA end-binding complex required for DNA double strand break repair and V(D)J recombination. Ku70(-/-) (K70T) mice, like recombination activating gene (RAG)-1- or RAG-2-deficient (R1T or R2T) mice, have impaired B and T cell development at an early progenitor stage, which is thought to result at least in part from defective V(D)J recombination (Gu, Y., K.J. Seidl, G.A. Rathbun, C. Zhu, J.P. Manis, N. van der Stoep, L. Davidson, H.L. Cheng, J.M. Sekiguchi, K. Frank, et al. 1997. Immunity. 7:653-665; Ouyang, H., A. Nussenzweig, A. Kurimasa, V.C. Soares, X. Li, C. Cordon-Cardo, W. Li, N. Cheong, M. Nussenzweig, G. Iliakis, et al. 1997. J. Exp. Med. 186:921-929). Therefore, to examine the potential role of Ku70 in CSR, we generated K70T mice that carry a germline Ig HC locus in which the JH region was replaced with a functionally rearranged VH(D)JH and Ig lambda light chain transgene (referred to as K70T/HL mice). Previously, we have shown that B cells from R1T or R2T mice carrying these rearranged Ig genes (R1T/HL or R2T/HL mice) can undergo CSR to IgG isotypes (Lansford, R., J. Manis, E. Sonoda, K. Rajewsky, and F. Alt. 1998. Int. Immunol. 10:325-332). K70T/HL mice had significant numbers of peripheral surface IgM+ B cells, which generated serum IgM levels similar to those of R2T/HL mice. However, in contrast to R2T/HL mice, K70T/HL mice had no detectable serum IgG isotypes. In vitro culture of K70T/HL B cells with agents that induce CSR in normal or R2T/HL B cells did lead to the induction of germline CH transcripts, indicating that initial signaling pathways for CSR were intact in K70T/HL cells. However, treatment with such agents did not lead to detectable CSR by K70T/HL B cells, and instead, led to cell death within 72 h. We conclude that Ku70 is required for the generation of B cells that have

  10. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  11. Higher Serum Levels of Free ĸ plus λ Immunoglobulin Light Chains Ameliorate Survival of Hemodialysis Patients

    DEFF Research Database (Denmark)

    Thilo, Florian; Caspari, Christina; Scholze, Alexandra

    2011-01-01

    Background/Aims: Impaired immune function is common in patients with chronic renal failure. Now, we determined whether serum levels of free immunoglobulin light chains predict mortality in patients with chronic kidney disease stage 5 on hemodialysis. Methods: We performed a prospective cohort study...... of 160 hemodialysis patients with a median follow-up of 15 months (interquartile range, 3-44 months). Serum levels of free κ and λ immunoglobulin light chains were measured at the start of the study. The primary end point was mortality from any cause. Results: In survivors, median serum levels of free κ...... plus λ immunoglobulin light chains were significantly higher compared with nonsurvivors (p light chains above the median compared with patients with serum levels below the median of 210 mg...

  12. Serum immunoglobulin levels in the ABCC-JNIH adult health study: Hiroshima and Nagasaki

    Energy Technology Data Exchange (ETDEWEB)

    King, R A; Milton, R C; Hamilton, H B

    1973-05-31

    Immunoglobulin levels (IgG, IgA, and IgM) were determined on 2043 individuals in the ABCC-JNIH Adult Health Study population, and levels were compared to disease states and the dose of radiation ATB. Mean levels for both cities and sexes combined were IgG = 1577 mg%, IgA = 312 mg%, and IgM = 127 mg%. Differences between these mean levels and those reported in other studies are thought secondary to racial and environmental factors, and technical differences with the methods used for quantitation. Females had higher IgM levels that tended to go down with advancing age. Of the diseases evaluated, rheumatoid arthritis, cirrhosis, and pulmonary tuberculosis affected immunoglobulin levels the greatest. There was no apparent relationship between radiation dose from the atomic bomb and immunoglobulin levels determined more than 25 years after exposure. (6 tables)

  13. Production and Purification Immunoglobulin against E. coli in Egg Yolk

    Directory of Open Access Journals (Sweden)

    Mohammadreza Nassiri

    2016-08-01

    Full Text Available Introduction Chicken is the only avian species in which polyclonal antibodies, like IgG is transported from the hen to the egg yolk in a similar manner as the transport of mammalian IgG from the mother to the fetus. Immunoglobulin Y in the chicken is transported to the egg and accumulates in the egg yolk in large quantities. IgY is an egg yolk antibody that has been used widely for treatment and prevention of infections in humans and animal. IgY is used for passive protection of the pathogen infections such as Escherichia coli, bovine and human rotavirus, bovine coronavirus, salmonella, staphylococcus and Pseudomonas. IgY is a promising candidate as an alternative to antibiotics. Eschericha coli strains of serotype O157: H7 belongs to a family of pathogenic E. coli called enterohemorrhagic E. coli (EHEC strains responsible for hemorrhagic colitis, bloody or non-bloody diarrhea, and hemolytic uremic syndrome in humans. This strain of E. coli pathogenises by adhering to host intestinal epithelium and forming bacterial colonies. The purpose of this study was to produce and purify immunoglobulin Y against E. coli O157:H7 and develop specific polyclonal anti E. coli antibody in the egg yolk. Materials and Methods Sixteen-week-old laying hens (Mashhad, Iran were kept in individual cages with food and water ad libitum. Immunization of hens was performed by intramuscularly injecting killed E. coli O157: H7 with an equal volume of Freund’s complete adjuvant into two sides of chest area (Sigma, USA for the first immunization. Two booster immunizations followed up using complete and incomplete Freund’s adjuvants in two weeks interval. Freund’s adjuvant without antigen was injected to the control group. Two weeks after the last injection, the eggs were collected daily for eight weeks, marked and stored at 4 ºC. In order to IgY purification, eggs were collected. Purification of IgY from egg yolk was based on Polson and using PEG6000. Finally, the

  14. Plasma vitamin D-binding protein (GC) factors, immunoglobulin G heavy chain (GM) allotypes and immunoglobulin kappa light chain (KM1) allotype in patients with sarcoidosis and in healthy control subjects

    DEFF Research Database (Denmark)

    Milman, Nils; Thymann, Mariann; Graudal, Niels

    2002-01-01

    BACKGROUND AND AIM: Sarcoidosis is an immune disease with abnormalities in the production of vitamin D and immunoglobulins. The aim was to examine whether the distribution of plasma vitamin D-binding protein = group-specific component (GC) allotypes, immunoglobulin G heavy chain (GM) allotypes an...

  15. Serum immunoglobulin levels predict fibrosis in patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    McPherson, Stuart; Henderson, Elsbeth; Burt, Alastair D; Day, Christopher P; Anstee, Quentin M

    2014-05-01

    A third of the population are estimated to have NAFLD of varying severity. Serum immunoglobulins are frequently elevated in patients with chronic liver disease, but little is known about serum immunoglobulin levels in patients with NAFLD. Aim of this study was to evaluate serum immunoglobulin levels (IgA, IgG, and IgM) in a large cohort of patients with biopsy-proven NAFLD and determine if immunoglobulin levels are associated with clinical or histological features. Patients seen in a tertiary fatty liver clinic between 1999 and 2009 were included. Liver biopsies were assessed using the Kleiner score. Immunoglobulin levels and other blood tests were taken at time of biopsy. 285 patients (110 simple steatosis and 175 NASH) had serum immunoglobulins measured within 6months of liver biopsy. 130 (46%) patients had elevated (>1× upper limit of normal) serum IgA levels, 28 (10%) patients had elevated IgG and 22 (8%) raised IgM. Serum IgA levels were elevated more frequently in patients with NASH compared with subjects with simple steatosis (55% vs. 31%, pliver fibrosis (Kleiner stage 3-4). There was a significant positive association between serum IgA levels and the stage of fibrosis (pfibrosis following multivariate analysis. A model constructed from these independent predictors accurately predicted advanced fibrosis (AUROC 0.87). The serum IgA level was frequently elevated in patients with NAFLD and was an independent predictor of advanced fibrosis. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  16. Computational study on the interactions and orientation of monoclonal human immunoglobulin G on a polystyrene surface

    Directory of Open Access Journals (Sweden)

    Javkhlantugs N

    2013-07-01

    Full Text Available Namsrai Javkhlantugs,1,2 Hexig Bayar,3 Chimed Ganzorig,1 Kazuyoshi Ueda2 1Center for Nanoscience and Nanotechnology and Department of Chemical Technology, School of Chemistry and Chemical Engineering, National University of Mongolia, Ulaanbaatar, Mongolia; 2Department of Advanced Materials Chemistry, Graduate School of Engineering, Yokohama National University, Yokohama, Japan; 3The Key Laboratory of Mammalian Reproductive Biology and Biotechnology of the Ministry of Education, Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, People's Republic of China Abstract: Having a theoretical understanding of the orientation of immunoglobulin on an immobilized solid surface is important in biomedical pathogen-detecting systems and cellular analysis. Despite the stable adsorption of immunoglobulin on a polystyrene (PS surface that has been applied in many kinds of immunoassays, there are many uncertainties in antibody-based clinical and biological experimental methods. To understand the binding mechanism and physicochemical interactions between immunoglobulin and the PS surface at the atomic level, we investigated the binding behavior and interactions of the monoclonal immunoglobulin G (IgG on the PS surface using the computational method. In our docking simulation with the different arrangement of translational and rotational orientation of IgG onto the PS surface, three typical orientation patterns of the immunoglobulin G on the PS surface were found. We precisely analyzed these orientation patterns and clarified how the immunoglobulin G interacts with the PS surface at atomic scale in the beginning of the adsorption process. Major driving forces for the adsorption of IgG onto the PS surface come from serine (Ser, aspartic acid (Asp, and glutamic acid (Glu residues. Keywords: bionano interface, immunoassay, polystyrene, IgG, physical adsorption, simulation

  17. On the Dark Side of Therapies with Immunoglobulin Concentrates: The Adverse Events

    OpenAIRE

    Sp?th, Peter J.; Granata, Guido; La Marra, Fabiola; Kuijpers, Taco W.; Quinti, Isabella

    2015-01-01

    Abstract to the dark side of therapies with human immunoglobulin G concentratesTherapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A p...

  18. Immunoglobulin transfusion in hemolytic disease of the newborn: place in therapy

    Directory of Open Access Journals (Sweden)

    Mundy CA

    2015-06-01

    Full Text Available Cynthia A Mundy, Jatinder Bhatia Department of Pediatrics, Division of Neonatology, Georgia Regents University, Children's Hospital of Georgia, GA, USA Abstract: Hemolytic disease of the newborn continues to be a common neonatal disorder that requires a comprehensive understanding on the part of those caring for infants. Common treatments include hydration and phototherapy. Exchange transfusion is used in severe hemolytic disease, but infants undergoing this treatment are exposed to many adverse effects. Intravenous immunoglobulin is a newer strategy that is showing promise in the treatment of the disease. This review discusses the current use and future expectations of intravenous immunoglobulin therapy in newborns. Keywords: hyperbilirubinemia, ABO incompatibility, neonatal jaundice 

  19. Intravenous Immunoglobulin therapy for anti-E hemolytic disease in the newborn.

    Science.gov (United States)

    Onesimo, Roberta; Rizzo, Daniela; Ruggiero, Antonio; Valentini, Piero

    2010-09-01

    Anti-E alloimmunisation is a less common cause of haemolytic disease in the newborn (HDN) and is usually associated with mild to moderate clinical manifestations, that are often less severe than anti-D immunisation. Conventional treatments for HDN are phototherapy and exchange transfusion, the latter still representing a high-risk procedure. Currently, intravenous immunoglobulin has been used as alternative treatment for HDN to reduce the need for exchange transfusion, as well as the length of phototherapy and hospitalisation. We report a case of anti-E HDN treated successfully with intravenous immunoglobulin, as adjuvant treatment to phototherapy.

  20. Serum immunoglobulin and complement levels in prematures with parenteral feeding--preliminary results.

    Science.gov (United States)

    Tamaro, G; Morena, C; Uxa, F; Candusso, M; Trappan, A; de Vonderweid, U

    1993-01-01

    Immunoglobulins IgA, IgG and IgM and complement factors C3 and C4 have been measured in a population of premature infants to evaluate their degree of immunological maturity. All the infants were receiving complete parenteral nutrition. In parallel, the same parameters were measured in twenty two full term, healthy neonates. To explore maturation and liver function, the authors used other proteins as nutritional markers. Differences in the immunoglobulins, but not in the complement fractions were seen between the two groups. Two applications are suggested: incidence of infections and post partum maturation.

  1. A study of immunoglobulins and complements (C3 &C4 in alopecia areata

    Directory of Open Access Journals (Sweden)

    Sharma R

    1995-01-01

    Full Text Available Estimation of serum Immunoglobulins (IgG, IgM and IgA and complements (C3 and C4 was carried out in 100 cases of alopecia areata as per method described by Mancini (1965.[1] Clinically patients were divided in two groups, alopecia areata circumscribed (group I and severe alopecia areata (group II. Significant decrease in levels of one or more Immunoglobulins were observed in most of the patients. However, Serum complements (C3 and C4 were within range of normal control values

  2. The relationship of age, anxiety, and serum immunoglobulins with crystallized and fluid intelligence.

    Science.gov (United States)

    Cohen, D; Eisdorfer, C; Vitaliano, P P; Bloom, V

    1980-10-01

    Serum immunoglobulin concentrations (IgG, IgA, and IgM), cognitive performance (crystallized and fluid intelligence), and self-reports of anxiety were evaluated in 24 men and women 60-75 years, and 50 men and women, 30-45 years. Trait anxiety was an important factor relating to performance differences between the young and old on crystallized and fluid subtests. IgM was inversely related to performance in the older age groups. Anxiety was not related to serum immunoglobulin levels.

  3. Estimation of serum, salivary immunoglobulin G, immunoglobulin A levels and total protein, hemoglobin in smokeless tobacco chewers and oral submucous fibrosis patients

    Directory of Open Access Journals (Sweden)

    Chandrakanth Balakrishnan

    2015-01-01

    Full Text Available Background: Oral submucous fibrosis (OSMF is a debilitating, potentially cancerous oral condition. Although areca nut is the most important causative agent, it is also considered that the disease is immunologically mediated. Aim of the Study: To establish that autoimmunity and nutritional deficiency play a role in the etiopathogenesis of OSMF. Objectives of the Study: To show that serum immunoglobulin markers (immunoglobulin-G [IgG], immunoglobulin-A [IgA] and nutritional parameters such as total serum protein (TSP, Hemoglobin (Hb play a role in causing OSMF and also to correlate serum, salivary IgG, IgA levels in OSMF patients. Settings and Design: A case-control study was done with 50 patients (25 patients who were provisionally diagnosed as OSMF - Group I, and 25 patients who were chronic smokeless tobacco chewers and who did not have any intraoral lesion - Group II. Materials and Methods: Five milliliters of blood and saliva were collected from both the groups. Quantitative analysis of serum, and salivary IgG, IgA was done by turbidometric immunoassay. TSP and Hemoglobin (Hb were estimated by spectrophotometry. Statistical Analysis: Results were analyzed by independent samples t-test and one-way analysis of variance (ANOVA. Results: All patients of OSMF showed significant (P < 0.01 increase in serum IgG, IgA, and salivary IgG levels as compared to smokeless tobacco chewers. The salivary IgA levels showed a significant decrease in OSMF patients (P < 0.05. TSP and Hb levels showed significant (P < 0.01 decrease in OSMF patients as compared to smokeless tobacco chewers. Conclusion: The elevation of immunoglobulin levels supports the concept of autoimmunity. The decrease in TSP and Hb suggests that nutritional deficiency plays a defined role in the occurrence as well as a further progression of OSMF.

  4. Development of an enzyme-linked immunosorbent assay for the detection of ciguatoxin in fish tissue using chicken immunoglobulin Y.

    Science.gov (United States)

    Empey Campora, Cara; Hokama, Yoshitsugi; Yabusaki, Kenichi; Isobe, Minoru

    2008-01-01

    A sandwich enzyme-linked immunosorbent assay was developed to detect ciguatoxin (CTX) in fish tissue. The assay utilizes two antibodies, chicken immunoglobulin Y specific to the ABCD domain of CTX and a mouse monoclonal immunoglobulin G-horseradish peroxidase conjugate specific to the JKLM domain of CTX. The sensitivity, working range, cross reactivity, accuracy, precision, and reproducibility were examined.

  5. N-linked glycosylation of the immunoglobulin variable region

    NARCIS (Netherlands)

    van de Bovenkamp, Fleur S.; Derksen, Ninotska I. L.; Ooijevaar-de Heer, Pleuni; van Schie, Karin A.; Kruithof, Simone; Berkowska, Magdalena A.; van der Schoot, C. Ellen; Ijspeert, Hanna; van der Burg, Mirjam; Gils, Ann; Hafkenscheid, Lise; Toes, René E. M.; Rombouts, Yoann; Plomp, Rosina; Wuhrer, Manfred; van Ham, S. Marieke; Vidarsson, Gestur; Rispens, Theo

    2018-01-01

    N-glycosylation sites are introduced at positions in which glycans can affect antigen binding as a result of a specific clustering of progenitor glycosylation sites in the germline sequences of variable domain genes. By analyzing multiple human monoclonal and polyclonal (auto)antibody responses, we

  6. Quantitation of Fc receptors and surface immunoglobulin is affected by cell isolation procedures using plasmagel and ficoll-hypaque.

    Science.gov (United States)

    Alexander, E L; Titus, J A; Segal, D M

    1978-01-01

    When mononuclear leukocytes are isolated directly from whole human blood using Ficoll-Hypaque or Plasmagel, cytophilic immunoglobulin is detected on cell surfaces. Upon incubation at 37 degrees C, this cell-associated immunoglobulin is shed slowly into the medium. However, when cells are prewashed in phosphate-buffered saline prior to isolation, they appear to be free of cytophilic immunoglobulin. Compared to prewashed cells, populations retaining cytophilic immunoglobulin on their surfaces demonstrate a decreased binding of soluble immune complexes and radiolabelled trimeric rabbit IgG. The data suggest that Ficoll-Hypaque and Plasmagel cause serum IgG to bind with abnormally high affinity to human mononuclear leukocytes, probably via Fc receptors. This artifact of preparation can lead to erroneous estimates of the numbers of cells bearing Fc receptors or intrinsic membrane immunoglobulin within a given population of cells and to an inaccurate assessment of the average number of Fc receptors per cell.

  7. Clearance of 131I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody

    International Nuclear Information System (INIS)

    Stewart, J.S.; Sivolapenko, G.B.; Hird, V.; Davies, K.A.; Walport, M.; Ritter, M.A.; Epenetos, A.A.

    1990-01-01

    Five patients treated with intraperitoneal 131I-labeled mouse monoclonal antibody for ovarian cancer also received i.v. exogenous polyclonal human anti-murine immunoglobulin antibody. The pharmacokinetics of 131I-labeled monoclonal antibody in these patients were compared with those of 28 other patients receiving i.p.-radiolabeled monoclonal antibody for the first time without exogenous human anti-murine immunoglobulin, and who had no preexisting endogenous human anti-murine immunoglobulin antibody. Patients receiving i.v. human anti-murine immunoglobulin antibody demonstrated a rapid clearance of 131I-labeled monoclonal antibody from their circulation. The (mean) maximum 131I blood content was 11.4% of the injected activity in patients receiving human anti-murine immunoglobulin antibody compared to 23.3% in patients not given human anti-murine immunoglobulin antibody. Intravenous human anti-murine immunoglobulin antibody decreased the radiation dose to bone marrow (from 131I-labeled monoclonal antibody in the vascular compartment) 4-fold. Following the injection of human anti-murine immunoglobulin antibody, 131I-monoclonal/human anti-murine immunoglobulin antibody immune complexes were rapidly transported to the liver. Antibody dehalogenation in the liver was rapid, with 87% of the injected 131I excreted in 5 days. Despite the efficient hepatic uptake of immune complexes, dehalogenation of monoclonal antibody was so rapid that the radiation dose to liver parenchyma from circulating 131I was decreased 4-fold rather than increased. All patients developed endogenous human anti-murine immunoglobulin antibody 2 to 3 weeks after treatment

  8. Using Mass Spectrometry to Quantify Rituximab and Perform Individualized Immunoglobulin Phenotyping in ANCA-Associated Vasculitis

    NARCIS (Netherlands)

    Mills, John R.; Cornec, Divi; Dasari, Surendra; Ladwig, Paula M.; Hummel, Amber M.; Cheu, Melissa; Murray, David L.; Willrich, Maria A.; Snyder, Melissa R.; Hoffman, Gary S.; Kallenberg, Cees G. M.; Langford, Carol A.; Merkel, Peter A.; Monach, Paul A.; Seo, Philip; Spiera, Robert F.; St Cair, E. William; Stone, John H.; Specks, Ulrich; Barnidge, David R.

    2016-01-01

    Therapeutic monoclonal immunoglobulins (mAbs) are used to treat patients with a wide range of disorders including autoimmune diseases. As pharmaceutical companies bring more fully humanized therapeutic mAb drugs to the healthcare market analytical platforms that perform therapeutic drug monitoring

  9. Fab glycosylation of immunoglobulin G does not associate with improvement of rheumatoid arthritis during pregnancy

    NARCIS (Netherlands)

    A. Bondt (Albert); M. Wuhrer (Manfred); T.M. Kuijper (Martijn); J.M.W. Hazes (Mieke); R.J.E.M. Dolhain (Radboud)

    2016-01-01

    textabstractBackground: Changes in immunoglobulin G (IgG) constant domain (Fc) glycosylation are associated with changes in rheumatoid arthritis (RA) disease activity in response to pregnancy. Here, we sought to determine whether the same holds true for variable domain (Fab) glycosylation. Methods:

  10. The use of bovine colostrum as a source of immunoglobulin (Ig) for ...

    African Journals Online (AJOL)

    The mean serum immunoglobulin (Ig) concentrations of both groups of lambs were determined at 6hr intervals during the first 48 hrs of life, using a pocket refractometer. There was no significant difference (P>0.05) in Ig levels between the bovine colostrum-fed lambs (21.01 zst units) and the normally suckled lambs (18.26 ...

  11. Immunoglobulin G4-related prostatitis: a case-control study focusing on clinical and pathologic characteristics

    NARCIS (Netherlands)

    Buijs, Jorie; Maillette de Buy Wenniger, Lucas; van Leenders, Geert; Verheij, Joanne; van Onna, Ilze; Hansen, Bettina; van Heerde, Marianne; Krak, Nanda; Beuers, Ulrich; Bruno, Marco; van Buuren, Henk

    2014-01-01

    To evaluate the occurrence and histopathologic characteristics of immunoglobulin G4 (IgG4)-related prostatic involvement in patients diagnosed with autoimmune pancreatitis. Nine cases of IgG4-related prostatitis were identified among 117 men in the autoimmune pancreatitis and IgG4-associated

  12. Immunoglobulin G4-related prostatitis: A case-control study focusing on clinical and pathologic characteristics

    NARCIS (Netherlands)

    J. Buijs (Jorie); L. Maillette De Buy Wenniger (Lucas); G.J.H.L. Leenders (Geert); J. Verheij (Joanne); I. van Onna (Ilze); B.E. Hansen (Bettina); M. van Heerde (Marianne); N.C. Krak (Nanda); U. Beuers (Ulrich); M.J. Bruno (Marco); H.R. van Buuren (Henk)

    2014-01-01

    markdownabstractOBJECTIVE To evaluate the occurrence and histopathologic characteristics of immunoglobulin G4 (IgG4)- related prostatic involvement in patients diagnosed with autoimmune pancreatitis. METHODS Nine cases of IgG4-related prostatitis were identified among 117 men in the

  13. On the dark side of therapies with immunoglobulin concentrates: the adverse events

    NARCIS (Netherlands)

    Späth, Peter J.; Granata, Guido; La Marra, Fabiola; Kuijpers, Taco W.; Quinti, Isabella

    2015-01-01

    Therapy by human immunoglobulin G (lgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase

  14. Mucosal immunoglobulins at respiratory surfaces mark an ancient association that predates the emergence of tetrapods

    DEFF Research Database (Denmark)

    Xu, Zhen; Takizawa, Fumio; Parra, David

    2016-01-01

    the first example of locally induced immunoglobulin in the mucosa of a cold-blooded species. Moreover, we demonstrate that gill microbiota is predominantly coated with IgT, thus providing previously unappreciated evidence that the microbiota present at a respiratory surface of a vertebrate is recognized...

  15. Genetic regulation of immunoglobulin E level in different pathological states: integration of mouse and human genetics

    Czech Academy of Sciences Publication Activity Database

    Gusareva, Elena; Kurey, Irina; Grekov, Igor; Lipoldová, Marie

    2014-01-01

    Roč. 89, č. 2 (2014), s. 375-405 ISSN 1464-7931 R&D Projects: GA ČR GA310/08/1697; GA MŠk LH12049 Institutional support: RVO:68378050 Keywords : Genetic control of complex diseases * Immunoglobulin E * Epistasis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.670, year: 2014

  16. An immunoenzymatic assay for the diagnosis of hepatitis A utilising immunoglobulin Y

    Directory of Open Access Journals (Sweden)

    Alexandre dos Santos da Silva

    2012-11-01

    Full Text Available The detection of anti-hepatitis A virus (HAV antibody levels by diagnostic kits in the convalescent period of disease generally use immunoglobulin G (IgG, which is expensive. An alternative to IgG is immunoglobulin Y (IgY, an immunoglobulin antibody encountered in birds and reptiles. The aim of this study was to develop a competitive immunoenzymatic assay to measure total anti-HAV antibody levels using anti-HAV IgY as the capture and conjugated immunoglobulins. For this purpose, anti-HAV IgY was conjugated to horseradish peroxidase (HRP and the optimal dilution of HRP-conjugated antibodies was evaluated to establish the competitive immuneenzymatic assay. The results obtained from our "in-house" assay were plotted on a receiver operator curve, which showed a sensitivity of 95% and a specificity of 98.8%, demonstrating that a competitive anti-HAV IgY immunoenzymatic assay developed "in house" could be used as an alternative to commercial assays that utilise IgG.

  17. Successive immunoglobulin and cytokine expression in the small intestine of juvenile chicken

    NARCIS (Netherlands)

    Lammers, A.; Wieland, W.H.; Kruijt, L.; Jansma, A.; Straetemans, T.; Schots, A.; Hartog, den C.G.; Parmentier, H.K.

    2010-01-01

    The intestinal mucosa is of major importance for immune development. To further study the ontogeny of avian mucosal immunity, mRNA levels of IgM, IgY and IgA, the polymeric immunoglobulin receptor (pIgR) and a number of cytokines were determined at different ages in jejunum and ileum of

  18. Chimeric immunoglobulin E reactive with tumor-associated antigen activates human Fc epsilon RI bearing cells

    NARCIS (Netherlands)

    Luiten, R. M.; Warnaar, S. O.; Schuurman, J.; Pasmans, S. G.; Latour, S.; Daëron, M.; Fleuren, G. J.; Litvinov, S. V.

    1997-01-01

    Crosslinking of immunoglobulin E molecules that are bound to the Fc epsilon receptors expressed on mast cells or basophils triggers activation of these cells, resulting in the development of a type I hypersensitivity. Targeting this potent immune reaction towards tumors by using IgE that reacts with

  19. Immunoglobulins of patients with idiopathic Addison's disease block the in vitro action of adrenocorticotropin

    NARCIS (Netherlands)

    Wulffraat, N. M.; Drexhage, H. A.; Bottazzo, G. F.; Wiersinga, W. M.; Jeucken, P.; van der Gaag, R.

    1989-01-01

    The presence of serum immunoglobulins (Ig) blocking ACTH-induced adrenal DNA synthesis and/or cortisol production was studied in 25 patients with idiopathic Addison's disease. For this purpose guinea pig adrenal segments kept in organ culture were exposed to ACTH and graded concentrations of patient

  20. A prospective study of nutritional status in immunoglobulin light chain amyloidosis

    DEFF Research Database (Denmark)

    Sattianayagam, PT; Lane, T; Fox, Z

    2013-01-01

    Weight loss is common in systemic immunoglobulin light chain amyloidosis but there are limited data on the impact of nutritional status on outcome. Using the Patient-Generated Subjective Global Assessment (PG-SGA) score, we prospectively examined nutritional status in 110 consecutive newly-diagno...

  1. Intravenous immunoglobulin in relapsing-remitting multiple sclerosis: a dose-finding trial

    DEFF Research Database (Denmark)

    Fazekas, F.; Lublin, F.D.; Li, D.

    2008-01-01

    OBJECTIVE: Several studies have reported a reduction of relapses after the long-term administration of IV immunoglobulin (IVIG) to patients with relapsing-remitting multiple sclerosis (RRMS), but they were mostly small and differed in terms of predefined outcome variables and treatment regimen. W...

  2. Immunoglobulin leakiness in scid mice with CD4(+) T-cell-induced chronic colitis

    DEFF Research Database (Denmark)

    Brimnes, J; Reimann, J; Claesson, Mogens Helweg

    2000-01-01

    Inflammatory bowel disease in scid mice is initiated by transplantation of CD4(+) T-cells from immunocompetent syngenic donor mice. As the disease progresses, immunoglobulin (Ig)-containing cells appear in the gut lamina propria, suggesting that locally accumulating Ig may play a role in disease ...

  3. A sensitive chain specific radioimmunoassay for human immunoglobulins using monoclonal antibodies

    International Nuclear Information System (INIS)

    Sikora, K.; Alderson, T.St.J.; Ellis, J.

    1983-01-01

    A sensitive radioimmunoassay is described for human immunoglobulins. This solid-phase assay uses commercially available monoclonal antibodies and is specific for different Ig chain types. Levels of less than 20 ng/ml Ig are detectable. The assay is suitable for the analysis of human hybridoma supernatants. (Auth.)

  4. The effect of chronic ammonia exposure on acute phase proteins, immunoglobulin and cytokines in laying hens

    Science.gov (United States)

    Ammonia is a potential health hazard to both humans and animals, causing systemic low-grade inflammation based on its levels and durations. The objective of this study was to examine the effect of 45 weeks of exposure to 30 ppm NH3 on the concentrations of acute phase proteins, immunoglobulins and c...

  5. Methods for the purification of equine rabies immunoglobulin: Effects on yield and biological activity

    NARCIS (Netherlands)

    H.A. Hong; E.J.M. Rooijakkers; N.T. Ke; J.M. Groen (Jan); A.D.M.E. Osterhaus (Albert)

    1994-01-01

    textabstractSince rabies is still a major cause of human death in many developing countries and the implementation of recommended post-exposure prophylaxis by vaccination and specific immunoglobulin therapy is largely hampered by its high cost, the development of cheap rabies vaccines and

  6. Circulating immune complexes, immunoglobulin classes (IgG, IgA ...

    African Journals Online (AJOL)

    Objective:- To evaluate serum levels of circulating immune complexes (CICs), immunoglobulin classes (IgG, IgA and IgM) and Complement Components (C3c, C4 and Factor B) in Nigerians with Type 1 or Type 2 diabetes mellitus. Design:- Case control study. Setting:- University College Hospital, Ibadan, Oyo State, Nigeria.

  7. Carotenoid supplementation and retinoic acid in immunoglobulin A regulation of the gut microbiota dysbiosis.

    Science.gov (United States)

    Lyu, Yi; Wu, Lei; Wang, Fang; Shen, Xinchun; Lin, Dingbo

    2018-04-01

    Dysbiosis, a broad spectrum of imbalance of the gut microbiota, may progress to microbiota dysfunction. Dysbiosis is linked to some human diseases, such as inflammation-related disorders and metabolic syndromes. However, the underlying mechanisms of the pathogenesis of dysbiosis remain elusive. Recent findings suggest that the microbiome and gut immune responses, like immunoglobulin A production, play critical roles in the gut homeostasis and function, and the progression of dysbiosis. In the past two decades, much progress has been made in better understanding of production of immunoglobulin A and its association with commensal microbiota. The present minireview summarizes the recent findings in the gut microbiota dysbiosis and dysfunction of immunoglobulin A induced by the imbalance of pathogenic bacteria and commensal microbiota. We also propose the potentials of dietary carotenoids, such as β-carotene and astaxanthin, in the improvement of the gut immune system maturation and immunoglobulin A production, and the consequent promotion of the gut health. Impact statement The concept of carotenoid metabolism in the gut health has not been well established in the literature. Here, we review and discuss the roles of retinoic acid and carotenoids, including pro-vitamin A carotenoids and xanthophylls in the maturation of the gut immune system and IgA production. This is the first review article about the carotenoid supplements and the metabolites in the regulation of the gut microbiome. We hope this review would provide a new direction for the management of the gut microbiota dysbiosis by application of bioactive carotenoids and the metabolites.

  8. Characterisation of an ELISA detecting immunoglobulin G to Mycobacterium avium subsp. paratuberculosis in bovine colostrum

    DEFF Research Database (Denmark)

    Zervens, Lisa Marie-Louise; Nielsen, Søren Saxmose; Jungersen, Gregers

    2013-01-01

    Although colostrum has been used to detect specific immunoglobulin (Ig) G to Mycobacterium avium subsp. paratuberculosis (MAP) in cattle, confounding, non-specific reactions can be a problem. The objectives of this study were to determine the proportion of non-specific ELISA reactions in samples...

  9. Development of a sandwich ELISA for quantification of immunoglobulin G in mink blood

    DEFF Research Database (Denmark)

    Mathiesen, Ronja; Chriél, Mariann; Struve, T.

    2016-01-01

    early immunity and thus their resistance against pathogenic agents found in the environment. This study describes a sandwich ELISA for quantification of the concentration of total immunoglobulin G in mink blood. The ELISA was validated with serum samples from females (n=8) and their kits (litters of 4...

  10. Adsorption of immunoglobulin G on core-shell latex particles precoated with chaps

    NARCIS (Netherlands)

    Giacomelli, CE; Vermeer, AWP; Norde, W

    2000-01-01

    The aim of this work is to investigate the adsorption behavior of a monoclonal antibody (immunoglobulin G, IgG) on latex particles, possessing reactive chloromethyl groups, precoated with 3-([3-cholamidopropyl]dimethylammonio-1-propansulfonate (Chaps). The amount and reactivity of the surface

  11. Adsorption of immunoglobulin G on core-shell latex particles precoated with chaps

    NARCIS (Netherlands)

    Giacomelli, C.E.; Vermeer, A.W.P.; Norde, W.

    2000-01-01

    The aim of this work is to investigate the adsorption behavior of a monoclonal antibody (immunoglobulin G, IgG) on latex particles, possessing reactive chloromethyl groups, precoated with 3-([3-cholamidopropyl]dimethylammonio-1-propanesulfonate (Chaps). The amount and reactivity of the surface

  12. Pulse methylprednisolone therapy for impending cardiac tamponade in immunoglobulin-resistant Kawasaki disease

    NARCIS (Netherlands)

    Dahlem, P. G.; von Rosenstiel, I. A.; Lam, J.; Kuijpers, T. W.

    1999-01-01

    We describe a boy with Kawasaki disease (KD) whose clinical course was marked by a rapid improvement upon treatment with intravenous immunoglobulin (IVIG) and oral aspirin, which - within 14 days - was followed by the development of a large pericardial effusion with symptoms of impending cardiac

  13. Normal human immunoglobulin G4 is bispecific: it has two different antigen-combining sites

    NARCIS (Netherlands)

    Schuurman, J.; van Ree, R.; Perdok, G. J.; van Doorn, H. R.; Tan, K. Y.; Aalberse, R. C.

    1999-01-01

    Unlike other immunoglobulin G (IgG) subclasses, IgG4 antibodies in plasma have been reported to be functionally monovalent. In this paper we show that the apparent monovalency of circulating IgG4 is caused by asymmetry of plasma IgG4. A large fraction of plasma IgG4 molecules have two different

  14. An evaluation of serum and tissue bound immunoglobulins in prostatic diseases.

    Directory of Open Access Journals (Sweden)

    Gahankari D

    1993-04-01

    Full Text Available In forty-four patients with different prostatic lesions serum immunoglobulins and tissue deposited immunoglobulins were studied by single radial immunodiffusion technique, and direct immunofluorescence and immunoperoxidase (PAP methods respectively. Serum IgM levels were found reduced only in patients with prostatic carcinomas (80% of cases as compared to controls. Serum IgA levels showed stage dependence in prostatic carcinoma being more raised in advanced malignancy (stage C and D than in localized ones (stage B. Localization of immunoglobulins particularly IgM, was characteristically found in stroma and lumen along with intracellular localization in prostatic carcinoma; while normal and benign lesions of prostate only showed characteristic ′necklace′ pattern. Also the intensity of deposits of immunoglobulins in poorly differentiated prostatic carcinomas was markedly low as compared to well differentiated carcinomas indicating lowered local immunological response in former. In prostatitis, IgA was also found localized in lumen indicating the immunological defence against infection by secretory antibody (IgA.

  15. Hemolytic anemia following high dose intravenous immunoglobulin in patients with chronic neurological disorders

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Christiansen, I; Harbo, Thomas

    2014-01-01

    High dose intravenous immunoglobulin (IVIG) is an established treatment for various neuromuscular disorders. Recently, cases of hemolytic anemia following IVIG have been observed. The objective of this study was to determine the extent of anemia and hemolysis after IVIG and its relationship...

  16. Interfacial behaviour of proteins, with special reference to immunoglobulins. A physicochemical study

    NARCIS (Netherlands)

    Norde, Willem; Lyklema, Johannes

    2012-01-01

    Some basic elements of the adsorption of proteins on solid surfaces are briefly reviewed, emphasizing immunoglobulins. The paper focuses on the physicochemical interactions and considers the precautions that have to be taken to let the protein adsorb in a way in which it is biologically active.

  17. IMMUNOGLOBULINS IN COLOSTRUM OF SOWS WITH PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME - PRRS

    Directory of Open Access Journals (Sweden)

    Michal ROLINEC

    2012-06-01

    Full Text Available The aim of this study was to examine the effect of PRRS occurrence on sow colostrum immunological quality. We realised the experiment on 20 sows (breed: Large white. From farm without presences of PRRS were 10 sows and other 10 sows were from farm with presence of PRRS. We took the samples of sows colostrums during sucking. We detected concentration of immunoglobulins (IgG, IgA, IgM in sows colostrum in time of 0 hours to 12 hours after beginning of farrowing with pig Ig ELISA quantitation kits. We determined statistically significant (P<0.01 higher concentration of IgG at the beginning of farrowing, 3 hours, 6 hours and 12 hours from beginning of farrowing in favour of farm without presence of PRRS. We determined statistically significant (P<0.01 higher concentration of IgA at 6 and 12 hours from beginning of farrowing in favour of farm without presence of PRRS. We determined statistically significant (P<0.01 higher concentration of IgM at 6 and 12 hours from beginning of farrowing in favour of farm without presence of PRRS. Lower concentrations of colostral immunoglobulins in group with PRRS can be caused of presence of PRRS. Virus PRRS can evocate synthesis of cytokine IL-10, which inhibited the function of macrophages and lymphocytes and so PRRS decrease the production of immunoglobulins and their concentration in blood of sows and consequently also concentration of immunoglobulins in sows colostrum.

  18. Evaluation of six immunoassays for detection of dengue virus-specific immunoglobulin M and G antibodies

    NARCIS (Netherlands)

    J. Groen (Jan); P. Koraka (Penelope); J. Velzing (Jans); C. Copra (Cederick); A.D.M.E. Osterhaus (Albert)

    2000-01-01

    textabstractThe performance of six commercially available immunoassay systems for the detection of dengue virus-specific immunoglobulin M (IgM) and IgG antibodies in serum was evaluated. These included two IgM and IgG enzyme immunoassays (EIA) from MRL Laboratories and PanBio, a rapid

  19. Nuclear positioning rather than contraction controls ordered rearrangements of immunoglobulin loci

    NARCIS (Netherlands)

    M.B. Rother (Magdalena); R.-J.T.S. Palstra (Robert-Jan); S. Jhunjhunwala (Suchit); K.A.M. Van Kester (Kevin A. M.); W.F.J. van IJcken (Wilfred); R.W. Hendriks (Rudi); J.J.M. van Dongen (Jacques); C. Murre (Cornelis); M.C. van Zelm (Menno)

    2016-01-01

    textabstractProgenitor-B cells recombine their immunoglobulin (Ig) loci to create unique antigen receptors. Despite a common recombination machinery, the Ig heavy and Ig light chain loci rearrange in a stepwise manner. We studied pre-pro-B cells and Rag-/- progenitor-B cells to determine whether Ig

  20. Association of killer cell immunoglobulin-like receptor polymorphisms with chronic hepatitis C and responses to therapy in Brazil

    Science.gov (United States)

    de Vasconcelos, Janaina Mota; de Jesus Maués Pereira Móia, Lizomar; Amaral, Ivanete do Socorro Abraçado; Miranda, Esther Castello Branco Mello; CicaliseTakeshita, Louise Yukari; de Oliveira, Layanna Freitas; de Araújo Melo Mendes, Lilian; Sastre, Danuta; Tamegão-Lopes, Bruna Pedroso; de Aquino Pedroza, Larysse Santa Rosa; Batista dos Santos, Sidney Emanuel; Soares, Manoel do Carmo Pereira; de Araújo, Marialva Tereza Ferreira; Bandeira, Camila Lucas; de Sousa da Silva, Adriana Maria Paixão; de Medeiros, Zilene Lameira; Sena, Leonardo; Demachki, Samia; dos Santos, Eduardo José Melo

    2013-01-01

    Soroprevalence for Hepatitis C virus is reported as 2.12% in Northern Brazil, with about 50% of the patients exhibiting a sustained virological response (SVR). Aiming to associate polymorphisms in Killer Cell Immunoglobulin-like Receptors (KIR) with chronic hepatitis C and therapy responses we investigated 125 chronic patients and 345 controls. Additionally, 48 ancestry markers were genotyped to control for population stratification. The frequency of the KIR2DL2 and KIR2DL2+HLA-CAsp80 gene and ligand was higher in chronic infected patients than in controls (p < 0.0009, OR = 3.4; p = 0.001, OR = 3.45). In fact, KIR2DL3 is a weaker inhibitor of NK activity than KIR2DL2, which could explain the association of KIR2DL2 with chronic infection. Moreover, KIR2DS2 and KIR2DS2+HLA-CAsp80 (p < 0.0001, OR = 2.51; p = 0.0084, OR = 2.62) and KIR2DS3 (p < 0.0001; OR = 2.57) were associated with chronic infection, independently from KIR2DL2. No differences in ancestry composition were observed between control and patients, even with respect to therapy response groups. The allelic profile KIR2DL2/KIR2DS2/KIR2DS3 was associated with the chronic hepatitis C (p < 0.0001; OR = 3). Furthermore, the patients also showed a higher mean number of activating genes and a lower frequency of the homozygous AA profile, which is likely secondary to the association with non-AA and/or activating genes. In addition, the KIR2DS5 allele was associated with SVR (p = 0.0261; OR = 0.184).The ancestry analysis of samples ruled out any effects of population substructuring and did not evidence interethnic differences in therapy response, as suggested in previous studies. PMID:23569404

  1. Association of killer cell immunoglobulin-like receptor polymorphisms with chronic hepatitis C and responses to therapy in Brazil

    Directory of Open Access Journals (Sweden)

    Janaina Mota de Vasconcelos

    2013-01-01

    Full Text Available Soroprevalence for Hepatitis C virus is reported as 2.12% in Northern Brazil, with about 50% of the patients exhibiting a sustained virological response (SVR. Aiming to associate polymorphisms in Killer Cell Immunoglobulin-like Receptors (KIR with chronic hepatitis C and therapy responses we investigated 125 chronic patients and 345 controls. Additionally, 48 ancestry markers were genotyped to control for population stratification. The frequency of the KIR2DL2 and KIR2DL2+HLA-C Asp80 gene and ligand was higher in chronic infected patients than in controls (p < 0.0009, OR = 3.4; p = 0.001, OR = 3.45. In fact, KIR2DL3 is a weaker inhibitor of NK activity than KIR2DL2, which could explain the association of KIR2DL2 with chronic infection. Moreover, KIR2DS2 and KIR2DS2+HLA-C Asp80 (p < 0.0001, OR = 2.51; p = 0.0084, OR = 2.62 and KIR2DS3 (p < 0.0001; OR = 2.57 were associated with chronic infection, independently from KIR2DL2. No differences in ancestry composition were observed between control and patients, even with respect to therapy response groups. The allelic profile KIR2DL2/KIR2DS2/KIR2DS3 was associated with the chronic hepatitis C (p < 0.0001; OR = 3. Furthermore, the patients also showed a higher mean number of activating genes and a lower frequency of the homozygous AA profile, which is likely secondary to the association with non-AA and/or activating genes. In addition, the KIR2DS5 allele was associated with SVR (p = 0.0261; OR = 0.184.The ancestry analysis of samples ruled out any effects of population substructuring and did not evidence interethnic differences in therapy response, as suggested in previous studies.

  2. Quantitative Analysis of Repertoire-Scale Immunoglobulin Properties in Vaccine-Induced B-Cell Responses

    Directory of Open Access Journals (Sweden)

    Ilja V. Khavrutskii

    2017-08-01

    Full Text Available Recent advances in the next-generation sequencing of B-cell receptors (BCRs enable the characterization of humoral responses at a repertoire-wide scale and provide the capability for identifying unique features of immune repertoires in response to disease, vaccination, or infection. Immunosequencing now readily generates 103–105 sequences per sample; however, statistical analysis of these repertoires is challenging because of the high genetic diversity of BCRs and the elaborate clonal relationships among them. To date, most immunosequencing analyses have focused on reporting qualitative trends in immunoglobulin (Ig properties, such as usage or somatic hypermutation (SHM percentage of the Ig heavy chain variable (IGHV gene segment family, and on reducing complex Ig property distributions to simple summary statistics. However, because Ig properties are typically not normally distributed, any approach that fails to assess the distribution as a whole may be inadequate in (1 properly assessing the statistical significance of repertoire differences, (2 identifying how two repertoires differ, and (3 determining appropriate confidence intervals for assessing the size of the differences and their potential biological relevance. To address these issues, we have developed a technique that uses Wilcox’ robust statistics toolbox to identify statistically significant vaccine-specific differences between Ig repertoire properties. The advantage of this technique is that it can determine not only whether but also where the distributions differ, even when the Ig repertoire properties are non-normally distributed. We used this technique to characterize murine germinal center (GC B-cell repertoires in response to a complex Ebola virus-like particle (eVLP vaccine candidate with known protective efficacy. The eVLP-mediated GC B-cell responses were highly diverse, consisting of thousands of clonotypes. Despite this staggering diversity, we identified statistically

  3. THE ROLE OF IgM-ENRICHED INTRAVENOUS IMMUNOGLOBULIN IN TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Szabó Judit

    2014-04-01

    Full Text Available After organ transplantation, gamma globulin and intravenous immunoglobulin enriched with IgM are most frequently used in septic shock as early immune-support. If the explanted organ is infected, the transplantation, as a life-saving operation, can be performed if there is no systemic inflammation and the patient receives IgM enriched immunoglobulin prophylaxis during surgery. The period after transplantation can be divided into three parts from the infection point of view: the first month after transplantation, the first sixth months and the following six months. Infections within the first month are basically related to the surgical procedure. Because of the immunosuppressive therapy, the opportunistic and fungal infections are more common during the first sixth months. After this period, the occurrence and the type of infections are similar to that of the non-transplant population except for pulmonary infections. The latter is two to three times more frequent. This is explained by the secondary hypogammaglobulinaemia (lower blood levels of IgM and IgG which is caused by the steroids but most of mycophenolate mofetil by inhibition of the T and B lymphocyte proliferation. Septic shock develops with a continuing fall of IgM levels. Under these circumstances additional intravenous immunoglobulin therapy with IgM can be lifesaving. Besides, immunoglobulin concentrates with IgM may also be used in the case of viral infections without prophylaxis and/or without etiological therapy such as in the case of West Nile virus infection. As a result of the increase in antibiotic resistance, the application of immunotherapy, including immunoglobulins may become the mainstream in the treatment of septic shock.

  4. Changes in serum immunoglobulin levels during radiotherapy for carcinoma of the uterine cervix

    International Nuclear Information System (INIS)

    Kaneta, Osamu

    1978-01-01

    We have, studied the effect of radiation on humoral immunity in patients with carcinoma of the cervix by measuring variations in serum immunoglobulins (IgA, IgG, IgM) during radiotherapy. Of 81 patients with untreated cancer of the cervix (at stages Ib-IIIb), those at stage III had a significantly lower IgG level (P < 0.05) compared with control patients (94 in number). There was a significant fall (P < 0.05) in the mean serum IgA and IgG levels during radiation therapy in group A (36 patients who received this modality of treatment alone). However, in group B (26 patients who underwent pelvic lymphadenectomy prior to radiotherapy) and in group C (9 patients subjected to hysterectomy with pelvic lymphadenectomy before irradiation) there was no significant fall in the mean serum IgA and IgG levels. There were two distinct patterns of variation in serum immunoglobulins seen during external irradiation: type a) in which serum immunoglobulin levels tended to decline with the increase in radiation dose, and type b) in which serum immunoglobulin levels either remained the same as those prior to irradiation or varied in an irregular fashion during irradiation. There was a significant difference (P < 0.05) in the incidence of either type a) or b) for IgG and IgM between group A and groups B and C. The type a) pattern of serum immunoglobulin variation was more common in patients with stage 1 carcinoma, and was gradually superceded by type b) in more advanced cases. Thus it would appear that lymph nodes retain the ability to respond to radiation in most cases of early stage carcinoma, but lose this capacity with more advanced carcinoma, a finding which is suggestive of lowered ability for antibody production of the most bearing advanced carcinoma. (author)

  5. Serum-derived bovine immunoglobulin/ protein isolate: postulated mechanism of action for management of enteropathy

    Directory of Open Access Journals (Sweden)

    Petschow BW

    2014-05-01

    Full Text Available Bryon W Petschow, Bruce Burnett, Audrey L Shaw, Eric M Weaver, Gerald L Klein Entera Health, Inc., Cary, NC, USA Abstract: The health and performance of the gastrointestinal tract is influenced by the interaction of a variety of factors, including diet, nutritional status, genetics, environment, stress, the intestinal microbiota, immune status, and gut barrier. Disruptions in one or more of these factors can lead to enteropathy or intestinal disorders that are known to occur in concert with certain disease states or conditions such as irritable bowel syndrome or human immunodeficiency virus (HIV infection. Nutritional support in the form of a medical food along with current therapies could help manage the adverse effects of enteropathy, which include effects on nutrient digestion, absorption, and metabolism, as well as utilization of nutrients from foodstuffs. Numerous studies have demonstrated that oral administration of plasma- or serum-derived protein concentrates containing high levels of immunoglobulins can improve weight management, normalize gut barrier function, and reduce the severity of enteropathy in animals. Recent trials in humans provide preliminary evidence that a serum-derived bovine immunoglobulin/protein isolate is safe and improves symptoms, nutritional status, and various biomarkers associated with enteropathy in patients with HIV infection or diarrhea-predominant irritable bowel syndrome. This review summarizes data from preclinical and clinical studies with immunoglobulin-containing plasma/serum protein concentrates, with a focus on the postulated mode of action of serum-derived bovine immunoglobulin/protein isolate for patients with enteropathy. Keywords: bovine immunoglobulins, nutrient, gut barrier, microbiota

  6. A fast universal immobilization of immunoglobulin G at 4 °C for the development of array-based immunoassays.

    Directory of Open Access Journals (Sweden)

    Shu-Lin Guo

    Full Text Available To maintain the antibody activity and enhance performance of array-based immunoassays, protein G was used to allow a shorter duration of immunoglobulin G immobilization at 4 °C, with the antibody placed in the appropriate orientation. The multiplexed detection of six pain-related message molecules (PRMMs was used as examples for the development of array-based immunoassays: substance P, calcitonin gene-related peptide, nerve growth factor, brain-derived neurotrophic factor, tumor necrosis factor-α, and β-endorphin. Protein G- and non-protein G-coated slides were tested. Compared to non-protein G immunoassays, protein G shortened the antibody immobilization time at 4 °C from overnight to 2 hours. Only protein G-facilitated immunoassays succeeded in simultaneously detecting all six PRMMs with high specificity. Dose-response curves showed that the limits of detection of the protein G-multiplexed immunoassays for the PRMMs was approximately 164, 167, 120, 60, 80, and 92 pg/ml, respectively. Thus, protein G effectively shortens the duration of antibody immobilization at 4 °C, allowing the use of sensitive array-based immunoassays for the simultaneous detection of PRMMs.

  7. Lack of immunoglobulin M suppression by immunoglobulin G antibody in thymectomized, irradiated, and bone marrow-reconstituted mice infected with Toxoplasma gondii.

    OpenAIRE

    Aryanpour, J; Hafizi, A; Modabber, F

    1980-01-01

    Thymectomized, irradiated, bone marrow-reconstituted (T-deprived) mie infected with an avirulent strain of Toxoplasma gondii produced antibody titers comparable to those produced in intact syngeneic mice. Both immunoglobulin M (IgM) and IgG antibodies were produced in T-deprived animals; however, the IgM antibody remained constant in the presence of increasing amounts of IgG. In the intact animals, IgM became undetectable by day 50 postinfection as expected. Feedback inhibition of IgM by IgG ...

  8. Lack of immunoglobulin M suppression by immunoglobulin G antibody in thymectomized, irradiated, and bone marrow-reconstituted mice infected with Toxoplasma gondii.

    Science.gov (United States)

    Aryanpour, J; Hafizi, A; Modabber, F

    1980-03-01

    Thymectomized, irradiated, bone marrow-reconstituted (T-deprived) mie infected with an avirulent strain of Toxoplasma gondii produced antibody titers comparable to those produced in intact syngeneic mice. Both immunoglobulin M (IgM) and IgG antibodies were produced in T-deprived animals; however, the IgM antibody remained constant in the presence of increasing amounts of IgG. In the intact animals, IgM became undetectable by day 50 postinfection as expected. Feedback inhibition of IgM by IgG seems to be dependent upon T-cells in Toxoplasma-infected mice.

  9. Gastric Cancer Associated Genes Identified by an Integrative Analysis of Gene Expression Data

    Directory of Open Access Journals (Sweden)

    Bing Jiang

    2017-01-01

    Full Text Available Gastric cancer is one of the most severe complex diseases with high morbidity and mortality in the world. The molecular mechanisms and risk factors for this disease are still not clear since the cancer heterogeneity caused by different genetic and environmental factors. With more and more expression data accumulated nowadays, we can perform integrative analysis for these data to understand the complexity of gastric cancer and to identify consensus players for the heterogeneous cancer. In the present work, we screened the published gene expression data and analyzed them with integrative tool, combined with pathway and gene ontology enrichment investigation. We identified several consensus differentially expressed genes and these genes were further confirmed with literature mining; at last, two genes, that is, immunoglobulin J chain and C-X-C motif chemokine ligand 17, were screened as novel gastric cancer associated genes. Experimental validation is proposed to further confirm this finding.

  10. Molecular mechanism of immunoglobulin V-region diversification regulated by transcription and RNA metabolism in antigen-driven B cells.

    Science.gov (United States)

    Sakaguchi, N; Maeda, K; Kuwahara, K

    2011-06-01

    The immune system produces specific antibodies (Ab) against any antigens (Ag) of exogenous and endogenous origins with a diverse repertoire of V-region specificities. The primary V-region repertoire is created by the rearrangement of immunoglobulin (Ig) V-region, D- and J-segments with the insertion of N- and P-sequences during early B cell differentiation. Recent studies revealed that secondary diversification of the IgV-region generated in the peripheral lymphoid organs plays a critical role in the generation of effective Ab production for protection from various pathogens. Naïve B cells that react with Ags initiate proliferation and differentiation in the follicular region and create the germinal centres (GCs), where activation-induced cytidine deaminase (AID)-dependent IgV-region somatic hypermutation (SHM) and class-switch recombination generate high-affinity and class-switched mature Ag-specific B cells. Our studies have discovered a 210-kDa nuclear protein, named GC-associated nuclear protein (GANP) that is up-regulated in GC B cells during the T cell-dependent (TD) immune responses. By studying mice with mutant forms of the ganp gene, we demonstrated that GANP is essential for the generation of high-affinity B cells against TD-Ag by affecting SHM at the IgV-regions. GANP is associated with AID in the cytoplasm and the GANP/AID complex is recruited to the nucleus, specifically, the chromatin, and targeted selectively to the IgV-region gene in B cells. GANP augments the access of AID towards IgV-regions in B cells. Here, we review the role of GANP in acquired immunity through the detailed analysis of the molecular mechanism generating SHM specifically at IgV-regions in B cells. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

  11. Diversification of the Primary Antibody Repertoire by AID-Mediated Gene Conversion.

    Science.gov (United States)

    Lanning, Dennis K; Knight, Katherine L

    2015-01-01

    Gene conversion, mediated by activation-induced cytidine deaminase (AID), has been found to contribute to generation of the primary antibody repertoire in several vertebrate species. Generation of the primary antibody repertoire by gene conversion of immunoglobulin (Ig) genes occurs primarily in gut-associated lymphoid tissues (GALT) and is best described in chicken and rabbit. Here, we discuss current knowledge of the mechanism of gene conversion as well as the contribution of the microbiota in promoting gene conversion of Ig genes. Finally, we propose that the antibody diversification strategy used in GALT species, such as chicken and rabbit, is conserved in a subset of human and mouse B cells.

  12. Genomic and transcriptomic comparison of allergen and silver nanoparticle-induced mast cell degranulation reveals novel non-immunoglobulin E mediated mechanisms.

    Science.gov (United States)

    Johnson, Monica; Alsaleh, Nasser; Mendoza, Ryan P; Persaud, Indushekhar; Bauer, Alison K; Saba, Laura; Brown, Jared M

    2018-01-01

    Mast cells represent a crucial cell type in host defense; however, maladaptive responses are contributing factors in the pathogenesis of allergic diseases. Previous work in our laboratory has shown that exposure to silver nanoparticles (AgNPs) results in mast cell degranulation via a non-immunoglobulin E (IgE) mechanism. In this study, we utilized a systems biology approach to identify novel genetic factors playing a role in AgNP-induced mast cell degranulation compared to the classical activation by antigen-mediated FcεRI crosslinking. Mast cell degranulation was assessed in bone marrow-derived mast cells isolated from 23 strains of mice following exposure to AgNPs or FcεRI crosslinking with dinitrophenyl (DNP). Utilizing strain-dependent mast cell degranulation, an association mapping study identified 3 chromosomal regions that were significantly associated with mast cell degranulation by AgNP and one non-overlapping region associated with DNP-mediated degranulation. Two of the AgNP-associated regions correspond to genes previously reported to be associated with allergic disorders (Trac2 on chromosome 1 and Traf6 on chromosome 2) and an uncharacterized gene identified on chromosome 1 (Fam126b). In conjunction, RNA-sequencing performed on mast cells from the high and low responder strains revealed 3754 and 34 differentially expressed genes that were unique to DNP and AgNP exposures, respectively. Select candidate genes include Ptger4, a gene encoding a G-protein coupled receptor in addition to a multifunctional adaptor protein, Txnip, that may be driving mast cell degranulation by AgNP. Taken together, we identified novel genes that have not been previously shown to play a role in nanoparticle-mediated mast cell activation. With further functional evaluation in the future, these genes may be potential therapeutic targets in the treatment of non-IgE mediated mast cell-linked disorders.

  13. Limited diagnostic capacities of two commercial assays for the detection of Leptospira immunoglobulin M antibodies in Laos

    NARCIS (Netherlands)

    Blacksell, Stuart D.; Smythe, Lee; Phetsouvanh, Rattanaphone; Dohnt, Michael; Hartskeerl, Rudy; SymondS, Meegan; Slack, Andrew; Vongsouvath, Manivanh; Davong, Viengmone; Lattana, Olay; Phongmany, Simmaly; Keolouangkot, Valy; White, Nicholas J.; Day, Nicholas P. J.; Newton, Paul N.

    2006-01-01

    The diagnostic utility of immunochromatographic (Leptotek) and enzyme-linked immunosorbent assay (ELISA; Panbio) tests for the detection of Leptospira immunoglobulin M antibodies was assessed in febrile adults admitted in Vientiane, Laos. Both tests demonstrated poor diagnostic accuracy using

  14. Detection and purification of rat and goat immunoglobulin G antibodies using protein G-based solid phase radioimmunoassays

    International Nuclear Information System (INIS)

    Nilson, B.; Aakerstroem, B.; Bjoerck, L.

    1986-01-01

    Using the newly described streptococcal surface protein, protein G, which has powerful immunoglobulin G binding properties, solid-phase radioimmunoassays were developed for the quantitation of goat and rat immunoglobulin G bound to the plastic surface of microtiter plates. The binding of goat immunoglobulin G to the surface via a specific antigen (guinea pig alpha 1 -microglobulin) permitted the determination of antigen-specific antibodies with a detection limit of 50-100 ng. Optimum assay conditions were established and the whole assay procedure could be brought to completion at room temperature in less than a working day. The value of the assays was illustrated by monitoring rat and goat immunoglobulin G antibodies during their purification from whole sera by classical chromatographic procedures. (Auth.)

  15. Fc-receptors and surface immunoglobulins in cells of the hairy cell leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Rieber, E P; Linke, R P; Riethmueller, G [Tuebingen Univ. (Germany, F.R.). Abt. fuer Experimentelle Chirurgie und Immunologie; Heyden, H.W. von; Waller, H D [Tuebingen Univ. (Germany, F.R.). Abt. Innere Medizin 2

    1976-01-01

    Using /sup 125/I-labelled aggregated IgG in a quantitative assay a strong expression of Fc-receptors was found on the leukemic cells of a patient with hairy cell leukemia. The Fc-receptor activity on these cells was much higher than that on monocytes and B-lymphocytes from normal blood. Surface immunoglobulins were detected by radioautography using radioactively labelled (Fab')/sub 2/-fragments of monospecific antibodies directed against immunoglobulin heavy chains. Prior to radioautography the cells were stained for the tartrate resistant acid phosphatase. It is found that all cells containing this enzyme bore delta-chains on their surface. On more than 90% of these cells a simultaneous expression of ..mu..-chains was detected. ..gamma..-chains could only be demonstrated on cells which were negative for the tartrate resistant acid phosphatase; part of these cells, however, were hairy cells by morphological criteria.

  16. Grasping the nettle: A bacterial invasin that targets immunoglobulin variable domains.

    Science.gov (United States)

    Barlow, Paul

    2018-06-01

    In a new paper, the protein InvD from Yersinia pseudotuberculosis , a zoonotic pathogen, is shown to assist late-stage invasion of intestinal epithelia. Remarkably, InvD acts by binding the Fab region of IgG or IgA. It straddles adjacent light-chain and heavy-chain variable domains, but its binding is different from that of antigens in that complementarity-determining regions do not participate. Structure determination revealed that its Fab-interacting domain adopts an immunoglobulin-like fold, fused to the preceding immunoglobulin-like domain and carried on a long stalk anchored to the bacterial outer membrane. Possible roles of this unusual host-pathogen interaction include avoidance of clearance from the intestine by secretory IgA. © 2018 Barlow.

  17. Structure of filamin A immunoglobulin-like repeat 10 from Homo sapiens

    International Nuclear Information System (INIS)

    Page, Richard C.; Clark, Jeffrey G.; Misra, Saurav

    2011-01-01

    The structure of immunoglobulin-like repeat 10 from human filamin A solved at 2.44 Å resolution suggests the potential effects of mutations correlated with otopalatodigital syndrome spectrum disorders. Filamin A (FlnA) plays a critical role in cytoskeletal organization, cell motility and cellular signaling. FlnA utilizes different binding sites on a series of 24 immunoglobulin-like domains (Ig repeats) to interact with diverse cytosolic proteins and with cytoplasmic portions of membrane proteins. Mutations in a specific domain, Ig10 (FlnA-Ig10), are correlated with two severe forms of the otopalatodigital syndrome spectrum disorders Melnick–Needles syndrome and frontometaphyseal dysplasia. The crystal structure of FlnA-Ig10 determined at 2.44 Å resolution provides insight into the perturbations caused by these mutations

  18. Overview of the pathogenesis and treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulins

    Directory of Open Access Journals (Sweden)

    Mohamed Mahdi-Rogers

    2010-03-01

    Full Text Available Mohamed Mahdi-Rogers, Yusuf A RajaballyNeuromuscular Clinic, Department of Neurology, University Hospitals of Leicester, Leicester, UKAbstract: Chronic inflammatory demyelinating polyneuropathy (CIDP is an acquired heterogeneous disorder of immune origin affecting the peripheral nerves, causing motor weakness and sensory symptoms and signs. The precise pathophysiology of CIDP remains uncertain although B and T cell mechanisms are believed to be implicated. Intravenous immunoglobulins (IVIg have been shown in a number of trials to be an effective treatment for CIDP. IVIg is thought to exert its immunomodulatory effects by affecting several components of the immune system including B-cells, T-cells, macrophages and complement. This article provides an overview of the pathogenesis of CIDP and of its treatment with IVIg.Keywords: chronic inflammatory demyelinating polyneuropathy, intravenous immunoglobulin, pathogenesis, treatment

  19. Fc-receptors and surface immunoglobulins in cells of the hairy cell leukemia

    International Nuclear Information System (INIS)

    Rieber, E.P.; Linke, R.P.; Riethmueller, G.; Heyden, H.W. von; Waller, H.D.

    1976-01-01

    Using 125 I-labelled aggregated IgG in a quantitative assay a strong expression of Fc-receptors was found on the leukemic cells of a patient with hairy cell leukemia. The Fc-receptor activity on these cells was much higher than that on monocytes and B-lymphocytes from normal blood. Surface immunoglobulins were detected by radioautography using radioactively labelled (Fab') 2 -fragments of monospecific antibodies directed against immunoglobulin heavy chains. Prior to radioautography the cells were stained for the tartrate resistant acid phosphatase. It is found that all cells containing this enzyme bore delta-chains on their surface. On more than 90% of these cells a simultaneous expression of μ-chains was detected. γ-chains could only be demonstrated on cells which were negative for the tartrate resistant acid phosphatase; part of these cells, however, were hairy cells by morphological criteria. (orig.) [de

  20. Intravenous Immunoglobulins: Mechanism of Action and Limitations of Clinical Application in Pediatrics

    Directory of Open Access Journals (Sweden)

    S.O. Mokiia-Serbina

    2016-02-01

    IVIG consumption is increasing due to the fact that in many cases the drugs are being used off-label. IVIG were more likely to be used in autoimmune and systemic inflammatory diseases. However, in randomized clinical trials, a good effect was achieved only in Kawasaki disease and immune thrombocytopenic purpura. Current clinical guidelines narrowed the indications for IVIG, limiting their use in sepsis. Immunoglobulin replacement therapy is recommended for children with physiological delay of immunoglobulin production only in repeated infections, which can not be controlled or prevented with antibiotics. In secondary ID, replacement therapy must be carried out if the cause of hypogammaglobulinemia can not be eliminated or elimination is contraindicated, as well as in association with β-cell cancers, in which severe infections caused by encapsulated bacteria persist despite preventive antibiotic therapy.

  1. [Value of intravenous immunoglobulins. A case of Guillain-Barré syndrome].

    Science.gov (United States)

    Hidou, M; Olivier, J; Vivant, J F

    1992-01-01

    A case of severe Guillain-Barré syndrome (GBS) was treated with high dose intravenous immunoglobulin (IVIG), 400 mg.kg-1.days-1, over three consecutive days. The treatment was repeated once. We observed a time-related response between immunoglobulins administration and clinical improvement. The pathologic lesions of the GBS suggest that this syndrome has an immunologic basis: a humoral factor is probably not the only immunological mechanism and cellular mechanisms are also likely to be of importance. Specific mechanisms might also be present in GBS, such as anti-idiotypic suppression of autoantibodies, and elimination of circulating immune complexes. Treatment with IVIG might have several therapeutic advantages over plasmapheresis: IVIG is easily infused without any delay, is easily available and has been used widely without serious complications.

  2. The Prospect of Immunoglobulin Y for Therapy of Canine parvovirus Infection in Dogs

    Directory of Open Access Journals (Sweden)

    I Gusti Ayu Agung Suartini

    2015-06-01

    Full Text Available Canine parvovirus (CPV is a highly infectious virus. The virus causes death in dogs worldwide. The mortality rate due to infection of CPV in dog reaches 91%. Prevention of CPV infection in puppies has been done by vaccination which is effectively proven. Protective mechanisms of maternal antibodies contribute to the failure of vaccination. Highly stable characteristics of parvovirus enable the virus still exist in the environment. Various therapies are performed only to suppress the clinical symptoms but can not reduce puppy mortalities. This review discusses CPV alternative therapy and the advantages using immunoglobulin Y (IgY specific antibodies isolated from chicken egg yolk. Immunoglobulin Y will neutralize the virus, so it can not infect host cells. Intravenous IgY therapy has shown to suppress the spread of CPV infection and prevent death.

  3. Injecting rabies immunoglobulin (RIG) into wounds only: A significant saving of lives and costly RIG.

    Science.gov (United States)

    Bharti, Omesh Kumar; Madhusudana, Shampur Narayan; Wilde, Henry

    2017-04-03

    An increasing number of dog bite victims were being presented to public hospitals in Himachal Pradesh in 2014 amidst virtual non availability of any rabies immunoglobulin (RIG). Only a small quantity of equine rabies immunoglobulin (eRIG) was available from the government owned Central Research Institute (CRI) Kasauli. This available eRIG was used in 269 patients as an emergency response and only for local infiltration of severe bite wounds by suspected rabid dogs. This was followed by rabies vaccination, using the WHO approved intra-dermal Thai Red Cross Society vaccination schedule. A subgroup of 26 patients were later identified who had been severely bitten by laboratory confirmed rabid dogs. They were followed for more than one year and all were found to be alive.

  4. Further studies of immunoglobulin synthesis by guinea-pig leukaemic lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hough, D W; Chapple, J C; Stevenson, F K; Stevenson, G T [Southampton General Hospital (UK)

    1978-05-01

    The L/sub 2/C leukemia is a B-lymphocytic neoplasm of strain 2 guinea pigs maintained by passaging in vivo. It synthesizes ..mu.. and lambda immunoglobulin chains. These combine to form monomeric (7S) IgM molecules which are inserted into the plasma membrane. From here they are shed as monomeric IgM and as a species of higher molecular weight which has not been further defined. The synthesis of lambda chain is in excess of that required for the IgM molecule, the surplus being exported directly from the cell without any intervening phase in the plasma membrane. Quantitative estimates of synthetic rates and pool sizes for these immunoglobulin species are presented.

  5. Induction of Regulatory T Cells by Intravenous Immunoglobulin: A Bridge between Adaptive and Innate Immunity.

    Science.gov (United States)

    Kaufman, Gabriel N; Massoud, Amir H; Dembele, Marieme; Yona, Madelaine; Piccirillo, Ciriaco A; Mazer, Bruce D

    2015-01-01

    Intravenous immunoglobulin (IVIg) is a polyclonal immunoglobulin G preparation with potent immunomodulatory properties. The mode of action of IVIg has been investigated in multiple disease states, with various mechanisms described to account for its benefits. Recent data indicate that IVIg increases both the number and the suppressive capacity of regulatory T cells, a subpopulation of T cells that are essential for immune homeostasis. IVIg alters dendritic cell function, cytokine and chemokine networks, and T lymphocytes, leading to development of regulatory T cells. The ability of IVIg to influence Treg induction has been shown both in animal models and in human diseases. In this review, we discuss data on the potential mechanisms contributing to the interaction between IVIg and the regulatory T-cell compartment.

  6. Detection of immunoglobulin M and immunoglobulin G antibodies to Mycoplasma pneumoniae in children with community-acquired lower respiratory tract infections

    Directory of Open Access Journals (Sweden)

    Surinder Kumar

    2018-01-01

    Full Text Available Context: Mycoplasma pneumoniae (M. pneumoniae causes up to 40% of community-acquired pneumonia in children. It is impossible to identify M. pneumoniae infection on the basis of clinical signs, symptoms, and radiological features. Therefore, correct etiological diagnosis strongly depends on laboratory diagnosis. Aims: This study aims to investigate the role of M. pneumonia e in pediatric lower respiratory tract infections (LRTIs employing enzyme-linked immunosorbent assays (ELISA and particle agglutination (PA test. Settings and Design: Two hundred and eighty children, age 6 months to 12 years with community-acquired LRTIs were investigated for M. pneumoniae etiology. Materials and Methods: We investigated 280 children hospitalized for community-acquired LRTIs, using ELISA and PA test for detecting M. pneumoniae immunoglobulin M (IgM and immunoglobulin G antibodies. Statistical Analysis Used: The difference of proportion between the qualitative variables was tested using the Chi-square test and Fischer exact test. P ≤ 0.05 was considered as statistically significant. Kappa value was used to assess agreement between ELISA and PA test. Results: M. pneumoniae was positive in 51 (23.2% 5 years of age.

  7. Production and purification of polyclonal antibody against F(ab')2 fragment of human immunoglobulin G

    OpenAIRE

    Nasiri, Hadi; Valedkarimi, Zahra; Aghebati-Maleki, Leili; Abdolalizadeh, Jalal; Kazemi, Tohid; Esparvarinha, Mojghan; Majidi, Jafar

    2017-01-01

    Antibodies are essential tools of biomedical and biochemical researches. Polyclonal antibodies are produced against different epitopes of antigens. Purified F(ab')2 can be used for animal’s immunization to produce polyclonal antibodies. Human immunoglobulin G (IgG) was purified by ion exchange chromatography method. In all stages verification method of the purified antibodies was sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Purified IgG was digested by pepsin enzyme a...

  8. Subcutaneous immunoglobulin in responders to intravenous therapy with chronic inflammatory demyelinating polyradiculoneuropathy

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Debost, J-C; Harbo, Thomas

    2013-01-01

    BACKGROUND AND PURPOSE: We hypothesized that subcutaneous administration of immunoglobulins (SCIG) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is feasible, safe and superior to treatment with saline for the performance of muscle strength. METHODS: Thirty patients with motor...... Research Council (MRC) score, grip strength, standardized electrophysiological recordings from three nerves, and plasma IgG levels were evaluated. RESULTS: SCIG treatment was well tolerated in all 14 patients. Six patients complained of mild side-effects at the injection site. In the SCIG group...

  9. Improved detection of a staphylococcal infection by monomeric and protein A-purified polyclonal human immunoglobulin

    International Nuclear Information System (INIS)

    Calame, W.

    1993-01-01

    The present study was undertaken to compare the technetium-99m labelled non-specific polyclonal human immunoglobulin (Ig) with 99m Tc-labelled monomeric human immunoglobulin (m-Ig), 99m Tc-labelled, protein A-purified, human immunoglobulin (A-IG) and 99m Tc-labelled monomeric, protein A-purified, human immunoglobulin (mA-Ig) as tracer agents for the detection of a thigh infection with Staphylococcus aureus. In vitro the binding of the various tracer agents to bacteria at various intervals was determined. For the in vivo evaluation, mice were infected and received one of the various labelled proteins. Scintigrams were made 0.25, 1, 4 and 24 h later. All 99m Tc-labelled Igs bound to bacteria in vitro: The percentages of binding for the m-Ig (from 1 h onwards) and A-Ig and mA-Ig (from 3 h onwards) were significantly higher than that for Ig. The in vivo target-to-non-target (T/NT) ratios were significantly higher from 4 h onwards for all purified Igs than for Ig. Protein A-purified Ig yielded higher T/NT ratios than m-Ig. Furthermore, the amount of activity in the liver was significantly lower 24 h after administration of m-Ig, A-Ig and mA-Ig than after administration of Ig. It is concluded that in this experimental infection 99m Tc-labelled monomeric Ig localizes a staphylococcal thigh infection better and faster than 99m Tc-labelled unpurified Ig. However, the accumulation obtained with protein A-purified Ig or protein A-purified monomeric Ig was the highest of all tracer agents tested. (orig.)

  10. [Comparative study of immunoglobulins and specific antibodies in the sera of chronic brucellosis patients].

    Science.gov (United States)

    Kichieva, B N; Chernysheva, M I; Zheludkov, M M; Musaeva, N B

    1982-04-01

    The data on the IgA, IgM and IgG levels in the sera of 89 patients with chronic brucellosis lasting for 1-10 years and longer are presented. The chronic form of brucellosis is characterized by the normal or low level of immunoglobulins. No correlation between the levels of IgG, IgM and the titer of specific antibodies has been established.

  11. Saccharomyces boulardii Stimulates Intestinal Immunoglobulin A Immune Response to Clostridium difficile Toxin A in Mice

    Science.gov (United States)

    Qamar, Amir; Aboudola, Samer; Warny, Michel; Michetti, Pierre; Pothoulakis, Charalabos; LaMont, J. Thomas; Kelly, Ciarán P.

    2001-01-01

    Saccharomyces boulardii is a nonpathogenic yeast that protects against antibiotic-associated diarrhea and recurrent Clostridium difficile colitis. The administration of C. difficile toxoid A by gavage to S. boulardii-fed BALB/c mice caused a 1.8-fold increase in total small intestinal immunoglobulin A levels (P = 0.003) and a 4.4-fold increase in specific intestinal anti-toxin A levels (P boulardii-mediated protection against diarrheal illnesses. PMID:11254650

  12. Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg?

    Directory of Open Access Journals (Sweden)

    Floriana Giorgio

    2015-09-01

    Full Text Available In the present narrative review, we analyzed the relationship between seronegative celiac disease (SNCD and immunoglobulin deficiencies. For this purpose, we conducted a literature search on the main medical databases. SNCD poses a diagnostic dilemma. Villous blunting, intraepithelial lymphocytes (IELs count and gluten “challenge” are the most reliable markers. Immunohistochemistry/immunofluorescence tissue transglutaminase (tTG-targeted mucosal immunoglobulin A (IgA immune complexes in the intestinal mucosa of SNCD patients may be useful. In our experience, tTG-mRNA was similarly increased in seropositive celiac disease (CD and suspected SNCD, and strongly correlated with the IELs count. This increase is found even in the IELs’ range of 15–25/100 enterocytes, suggesting that there may be a “grey zone” of gluten-related disorders. An immune deregulation (severely lacking B-cell differentiation underlies the association of SNCD with immunoglobulin deficiencies. Therefore, CD may be linked to autoimmune disorders and immune deficits (common variable immunodeficiency (CVID/IgA selective deficiency. CVID is a heterogeneous group of antibodies dysfunction, whose association with CD is demonstrated only by the response to a gluten-free diet (GFD. We hypothesized a familial inheritance between CD and CVID. Selective IgA deficiency, commonly associated with CD, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD is rare (<300 cases and associated to CD in 5% of cases. We diagnosed SNCD in a patient affected by sIgMD using the tTG-mRNA assay. One-year GFD induced IgM restoration. This evidence, supporting a link between SNCD and immunoglobulin deficiencies, suggests that we should take a closer look at this association.

  13. Utilization of newly developed immobilized enzyme reactors for preparation and study of immunoglobulin G fragments

    Czech Academy of Sciences Publication Activity Database

    Korecká, L.; Bílková, Z.; Holčapek, M.; Královský, J.; Beneš, Milan J.; Lenfeld, Jiří; Minc, N.; Cecal, R.; Viovy, J.-L.; Przybylski, M.

    2004-01-01

    Roč. 808, č. 1 (2004), s. 15-24 ISSN 1570-0232. [International Symposium on Polymer Design for BioSeparation and Nanobiotechnology /8./. Compiegne, 27.11.2003-29.11.2003] Grant - others:GA ČR(CZ) GA203/02/0023 Program:GA Institutional research plan: CEZ:AV0Z4050913 Keywords : immobilized enzyme reactors * immunoglobulin G Subject RIV: CE - Biochemistry Impact factor: 2.176, year: 2004

  14. Perforated Appendicitis After Intravenous Immunoglobulin Therapy in a Term Neonate with Haemolytic Jaundice

    International Nuclear Information System (INIS)

    Atikan, B. Y.; Koroglu, O. A.; Yalaz, M.; Ergun, O.; Dokumcu, Z.; Doganavasrgil, B.

    2015-01-01

    Neonatal appendicitis is a rare clinical condition that may cause high morbidity and mortality if diagnosis is delayed. There is usually an underlying disease; it can also be a localized form of necrotizing enterocolitis. Here, we present a term neonate who was treated with intravenous immunoglobulin because of severe isoimmune hemolytic jaundice. The patient developed abdominal symptoms within 10 hours of therapy, was diagnosed with acute perforated appendicitis and completely recovered after surgery. (author)

  15. Grave′s disease associated with immunoglobulin A nephropathy: A rare association

    OpenAIRE

    I Khan; R A Bhat; I Khan; I Hameed

    2015-01-01

    Immunoglobulin A (Ig A) nephropathy is the most common form of primary glomerulonephritis. The association of Ig A nephropathy with Grave's disease has not been reported so far. We report a case of 20-year-old female with Grave's disease who presented with edema, facial puffiness, and decreased urine output. She was found to be hypertensive with renal failure and nephrotic range proteinuria. Renal biopsy revealed features of Ig A nephropathy. The patient was treated with oral corticosteroids ...

  16. A case of coombs-positive severe late anemia without hyperbilirubinemia, refractory to blood transfusion, improved with immunoglobulin

    Directory of Open Access Journals (Sweden)

    Supriya Kushwah

    2017-01-01

    Full Text Available Rhesus hemolytic disease of newborn is a well-known disease with early and late complications mainly manifesting as severe hyperbilirubinemia requiring prompt treatment such as exchange transfusion and immunoglobulins. We report a case of Coombs-positive severe late anemia without hyperbilirubinemia which presented with features such as sepsis and failure to gain weight. Baby was refractory to blood transfusion initially, but later on successfully improved with immunoglobulins.

  17. PARTIAL PURIFICATION AND IMMUNE-BIOCHEMICAL CHARACTERIZATION OF ROYAL BENGAL TIGER ( PANTHERA TIGRIS TIGRIS SERUM IMMUNOGLOBULIN G

    Directory of Open Access Journals (Sweden)

    Ekantika Mandal

    2013-12-01

    Full Text Available In the present study Immunoglobulin G was purified from serum of Royal Bengal Tiger by gel filtration chromatography on Sephacryl S-200. SDS-PAGE analysis showed the molecular weight of purified tiger IgG was 170.52 kDa. The purified Immunoglobulin has been found to be immunereactive by DID test and Western Blot analysis when treated against hyperimmune sera which was raised in rabbit.

  18. Importance of killer immunoglobulin-like receptors in allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Danilo Santana Alessio Franceschi

    2011-01-01

    Full Text Available Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein.

  19. Characterisation of up-regulated immunoglobulins in patients with chronic rhinosinusitis

    International Nuclear Information System (INIS)

    Madani, S.A.; Hashemi, S.A

    2014-01-01

    To evaluate the role of immunoglobulins in patients of chronic rhinosinusitis. Methods: Patients were recruited from the Ear, Nose, Throat, Head And Neck Surgery section of Mazandaran University of Medical Sciences, Sari, Iran, from December 2011 to August 2012. Immunoglobulin G, IgG1, IgG2, IgG3, IgG4 were evaluated. Salivary IgA was assessed by direct immunoenzymatic determination. The quantifications of serum IgG, IgG1, IgG2, IgG3, IgG4 and salivary IgA was performed through nephelometric procedure. Serum IgE was measured by enzyme-linked immunoabsorbent assay. SPSS 15 was used for statistical analysis. Results: Of the 50 patients, 22 (44%) were males and 28(56%) were females. The overall age ranged from 1 to 67 years with a mean of 28.06+-15.49. There was significant changes in levels of IgG, IgG1, salivary IgA and IgE (p=0.001). Significant difference was noted for IgG2 (p=0.03) and in IgG4 (p=0.01). There was no significant alteration in IgG3 level (p=0.3). Conclusion: There was high prevalence of humoral immune alterations both in local and systemic response to chronic inflammation in the patients, which suggests that assessment of immunoglobulin before clinical evaluation and management could be important. (author)

  20. Serum immunoglobulin from Nellore cattle produced by in vitro fertilization and treated for umbilical diseases

    Directory of Open Access Journals (Sweden)

    Celso Antonio Rodrigues

    Full Text Available ABSTRACT: The aim of this study was to measure serum immunoglobulin concentrations of Nellore cattle produced by in vitro fertilization (IVF with umbilical diseases and to evaluate surgical excision as a method of treatment. Sixteen cattle with ages ranging from 1 to 15 months, males and females, affected by umbilical diseases were enrolled in the study. Blood samples were collected for cell counts and the determination of immunoglobulin concentrations by electrophoresis and zinc sulphate turbidimetry (ZST. Four calves were presented with umbilical herniation, two with an umbilical herniation associated with a persistent urachus, two with an umbilical herniation with a persistent urachus and omphaloarteritis, three with an umbilical herniation and an urachal diverticulum, three with a persistent urachus, one with an urachal diverticulum, and one with omphalitis. The blood cell counts pre- and post-surgical revealed differences in cell volume and the number of leukocytes. The immunoglobulin values measured by electrophoresis values were below normal in most animals, whereas the ZST showed normal levels in most of them. Most of the calves affected by umbilical diseases and produced by IVF presented hypoglobulinaemia. Correlations between umbilical diseases, failure of passive transfer of immunity and IVF could not be demonstrated.

  1. Generation and Characterization of Polyclonal Antibody Against Part of Immunoglobulin Constant Heavy υ Chain of Goose

    Science.gov (United States)

    Zhao, Panpan; Guo, Yongli; Ma, Bo; Wang, Junwei

    2014-01-01

    Immunoglobulin Y (abbreviated as IgY) is a type of immunoglobulin that is the major antibody in bird, reptile, and lungfish blood. IgY consists of two light (λ) and two heavy (υ) chains. In the present study, polyclonal antibody against IgYFc was generated and evaluated. rIgYCυ3/Cυ4 was expressed in Escherichia coli, purified and utilized to raise polyclonal antibody in rabbit. High affinity antisera were obtained, which successfully detected the antigen at a dilution of 1:204,800 for ELISA assay. The antibody can specifically recognize both rIgYCυ3/Cυ4 and native IgY by Western bolt analysis. Furthermore, the serum of Grus japonensis or immunoglobulin of chicken, duck, turkey, and silkie samples and dynamic changes of serum GoIgY after immunogenicity with GPV-VP3-virus-like particles (GPV-VP3-VLPs) can be detected with the anti-GoIgYFc polyclonal antibody. These results suggested that the antibody is valuable for the investigation of biochemical properties and biological functions of GoIgY. PMID:25171010

  2. Production of immunoglobulins in gingival tissue explant cultures from juvenile periodontitis patients

    International Nuclear Information System (INIS)

    Hall, E.R.; Falkler, W.A. Jr.; Suzuki, J.B.

    1990-01-01

    B lymphocytes and plasma cells are histologically observed in granulomatous periodontal tissues of juvenile periodontitis (JP) patients. Local immune processes may participate in protective or immunopathologic roles in the pathogenesis of this disease. An in vitro explant culture system was utilized to demonstrate the production of immunoglobulins by diseased JP tissues. Immunodiffusion studies using goat anti-human gamma, alpha, or mu chain serum revealed IgG to be the major immunoglobulin present in 92% of the day 1 supernatant fluids (SF) of the 47 JP gingival tissue explant cultures. IgA was present in 15% of the SF; however, no IgM was detected. Staph Protein A isolated 14C-labeled IgG from the SF, when allowed to react with goat anti-human gamma chain serum, formed lines of precipitation. Positive autoradiographs confirmed the biosynthesis of IgG by the explant cultures. The in vitro gingival tissue explant culture system described provides a useful model for the study of localized immunoglobulins produced by diseased tissues of JP patients

  3. Collaborative study for the validation of alternative in vitro potency assays for human tetanus immunoglobulins.

    Science.gov (United States)

    Gross, S; Janssen, S W J; de Vries, B; Terao, E; Daas, A; Buchheit, K-H

    2010-07-01

    An international collaborative study to validate 2 alternative in vitro methods for the potency testing of human tetanus immunoglobulin products was organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM). The study, run in the framework of the Biological Standardisation Programme (BSP) under the aegis of the European Commission and the Council of Europe, involved 21 official medicines control and industry laboratories from 15 countries. Both methods, an enzyme-linked immunoassay (EIA) and a toxoid inhibition assay (TIA), showed good reproducibility, repeatability and precision. EIA and TIA discriminated between low, medium and high potency samples. Potency estimates correlated well and both values were in close agreement with those obtained by in vivo methods. Moreover, these alternative methods allowed to resolve discrepant results between laboratories that were due to product potency loss and reporting errors. The study demonstrated that EIA and TIA are suitable quality control methods for tetanus immunoglobulin, which can be standardised in a control laboratory using a quality assurance system. Consequently, the Group of Experts on Human Blood and Blood Products of the European Pharmacopoeia revised the monograph on human tetanus immunoglobulins to include both the methods as compendial alternatives to the in vivo mouse challenge assay. 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

  4. Constant region of a kappa III immunoglobulin light chain as a major AL-amyloid protein

    DEFF Research Database (Denmark)

    Engvig, J P; Olsen, K E; Gislefoss, R E

    1998-01-01

    AL-amyloidoses are generally described as a group of disorders in which N-terminal fragments of monoclonal immunoglobulin light chains are transferred into amyloid fibrils. We have, by amino acid sequence analyses and immunological methods, characterized the Bence-Jones protein and the correspond......AL-amyloidoses are generally described as a group of disorders in which N-terminal fragments of monoclonal immunoglobulin light chains are transferred into amyloid fibrils. We have, by amino acid sequence analyses and immunological methods, characterized the Bence-Jones protein...... and the corresponding AL protein as a kappa III immunoglobulin light chain from material of a patient with systemic AL-amyloidosis presenting as a local inguinal tumour. The two proteins showed some unique features. The major part of the AL amyloid fibril protein consisted of C-terminal fragments of the Bence......-Jones protein. Furthermore, both the Bence-Jones protein and the AL protein were glycosylated, with possibly a glycosylation in the constant part of the light chain....

  5. Serum immunoglobulin levels in humans exposed to therapeutic total-body gamma irradiation

    International Nuclear Information System (INIS)

    Chaskes, S.; Kingdon, G.C.; Balish, E.

    1975-01-01

    Reduced serum immunoglobulin (IgA, IgG, IgM) levels developed in the majority of 27 patients with hematologic disorders after treatment with 100 to 350 R total-body gamma-ray exposures at a dose rate of either 1.5 R/min to 1.5 R/hr. A reduction in IgA of 20 percent or more was found in 66 percent of the cases, while 56 percent showed an IgM decrease, and 49 percent an IgG decrease of 20 percent. The severity of immunoglobulin depression was influenced by the total radiation dose and the patient's primary disease. The occurrence of IgG and IgM depression was greater when the radiation was given at 1.5 R/hr than when the dose rate was 1.5 R/min. Substantial but incomplete recovery toward preirradiation immunoglobulin levels was found for most patients by 7 wk after total-body irradiation (TBI). (U.S.)

  6. Influence of column type and chromatographic conditions on the ion-exchange chromatography of immunoglobulins.

    Science.gov (United States)

    Yang, Y B; Harrison, K

    1996-08-30

    Immunoglobulins are often purified by affinity chromatography. However, this technique is costly, can result in poor resolution for subclasses (or is only group specific), and leads to possible leaching of contaminants into the purified products. Ion-exchange chromatography has shown great potential and has found an increased usage in the purification of immunoglobulins. The aim of this study is to further understand the separation mechanism with emphasis on the influence of column type and chromatographic conditions on the peak shape, selectivity and changes in the elution patterns. Included are strong cation-exchange, strong anion-exchange and weak anion-exchange columns. Five immunoglobulin G antibodies were used as test probes. Some sera and ascites were also used in the study. Among the chromatographic conditions examined were mobile phase pH, buffer type, buffer concentration, gradient rate, and column temperature. Significant differences in the chromatographic behavior (elution pattern, peak shape and selectivity) of the test samples are discussed in regard to the column type and the chromatographic conditions.

  7. Clinical Efficiency of Application of Intravenous Immunoglobulin in Pregnant Women with Intrauterine Infection

    Directory of Open Access Journals (Sweden)

    O.L. Ishchenko

    2016-02-01

    Full Text Available The problem of intrauterine infection (IUI is still relevant today. Ineffective treatment of this pathology is associated with physiological decline of the immunity in these patients. We have proposed the additional use of intravenous immunoglobulin for the treatment of pregnant women with IUI. There were examined 75 patients with IUI, which was diagnosed in the II trimester. The I group consisted of 40 individuals who received conventional treatment, the II group was formed from 35 women who additionally received intravenous immunoglobulin. On the background of IUI, pregnancy was characterized by an increased incidence of threatened miscarriage and premature labor, gestosis and placental dysfunction; during delivery, premature rupture of amniotic membrane and fetal distress were more common. These patients had placenta with both ultrasonic and histological signs of infection. Among newborns, there was a significant increase in the incidence of pathology associated with intrauterine infection. Additional use of intravenous immunoglobulin in the treatment of IUI during the II trimester of pregnancy in comparison with conventional therapy leads to a significant reduction in the incidence of both obstetric complications and perinatal pathology.

  8. The pH of chemistry assays plays an important role in monoclonal immunoglobulin interferences.

    Science.gov (United States)

    Alberti, Michael O; Drake, Thomas A; Song, Lu

    2015-12-01

    Immunoglobulin paraproteins can interfere with multiple chemistry assays. We want to investigate the mechanisms of immunoglobulin interference. Serum samples containing paraproteins from the index patient and eight additional patients were used to investigate the interference with the creatinine and total protein assays on the Beckman Coulter AU5400/2700 analyzer, and to determine the effects of pH and ionic strength on the precipitation of different immunoglobulins in these patient samples. The paraprotein interference with the creatinine and total protein assays was caused by the precipitation of IgM paraprotein in the index patient's samples under alkaline assay conditions. At extremely high pH (12-13) and extremely low pH (1-2) and low ionic strength, paraprotein formed large aggregates in samples from the index patient but not from other patients. The pH and ionic strength are the key factors that contribute to protein aggregation and precipitation which interfere with the creatinine and total protein measurements on AU5400/2700. The different amino acid sequence of each monoclonal paraprotein will determine the pH and ionic strength at which the paraprotein will precipitate.

  9. Production of immunoglobulins in gingival tissue explant cultures from juvenile periodontitis patients

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    Hall, E.R.; Falkler, W.A. Jr.; Suzuki, J.B. (Univ. of Maryland Dental School, Baltimore (USA))

    1990-10-01

    B lymphocytes and plasma cells are histologically observed in granulomatous periodontal tissues of juvenile periodontitis (JP) patients. Local immune processes may participate in protective or immunopathologic roles in the pathogenesis of this disease. An in vitro explant culture system was utilized to demonstrate the production of immunoglobulins by diseased JP tissues. Immunodiffusion studies using goat anti-human gamma, alpha, or mu chain serum revealed IgG to be the major immunoglobulin present in 92% of the day 1 supernatant fluids (SF) of the 47 JP gingival tissue explant cultures. IgA was present in 15% of the SF; however, no IgM was detected. Staph Protein A isolated 14C-labeled IgG from the SF, when allowed to react with goat anti-human gamma chain serum, formed lines of precipitation. Positive autoradiographs confirmed the biosynthesis of IgG by the explant cultures. The in vitro gingival tissue explant culture system described provides a useful model for the study of localized immunoglobulins produced by diseased tissues of JP patients.

  10. The frequencies of Killer immunoglobulin-like receptors and their HLA ligands in chronic inflammatory demyelinating polyradiculoneuropathy are similar to those in Guillian Barre syndrome but differ from those of controls, suggesting a role for NK cells in pathogenesis.

    Science.gov (United States)

    Blum, Stefan; Csurhes, Peter; McCombe, Pamela

    2015-08-15

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired inflammatory neuropathy, which has similar clinical and pathological features to Guillain-Barré Syndrome (GBS), but differs in time course. We investigated the frequency of genes encoding Killer immunoglobulin-like receptors and their HLA ligands in subjects with CIDP, in subjects with GBS and in healthy controls. There were no differences in KIR gene frequency among the 3 groups. The gene frequencies for HLA-B Bw4-I were significantly greater in CIDP than HC, but did not differ from GBS. The frequency of the combination of 3DL1/HLA-B Bw4I was greater in CIDP than HC, but did not differ from that of GBS. These data raise the possibility of NK cell function being an important factor in the pathogenesis of CIDP. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle.

    Directory of Open Access Journals (Sweden)

    Akiko Sano

    Full Text Available Therapeutic human polyclonal antibodies (hpAbs derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc cattle carrying a human artificial chromosome (HAC comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH and kappa-chain (hIGK germline loci (named as κHAC are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO. However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ in the pre-B cell receptor (pre-BCR complex, we partially replaced (bovinized the hIgM constant domain with the counterpart of bovine IgM (bIgM that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO, the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG can be produced from such Tc cattle.

  12. Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps.

    Science.gov (United States)

    Song, Jia; Wang, Hai; Zhang, Ya-Na; Cao, Ping-Ping; Liao, Bo; Wang, Zhe-Zheng; Shi, Li-Li; Yao, Yin; Zhai, Guan-Ting; Wang, Zhi-Chao; Liu, Li-Meng; Zeng, Ming; Lu, Xiang; Wang, Heng; Yang, Xiang-Ping; Yu, Di; Bachert, Claus; Liu, Zheng

    2018-03-01

    The contribution of ectopic lymphoid tissues (eLTs) to local immunoglobulin hyperproduction in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear. We sought to explore the cellular basis, formation mechanisms, and function of eLTs in patients with CRSwNP. We graded lymphoid aggregations in sinonasal mucosa and histologically studied their structures. The expression of lymphorganogenic factors and molecules required for immunoglobulin production was measured by using real-time PCR, and their localization was analyzed by means of immunohistochemistry and immunofluorescence. The phenotype of follicular helper T cells was analyzed by performing flow cytometry. Immunoglobulin levels were quantified by using the Bio-Plex assay or ImmunoCAP system. Nasal tissue explants were challenged ex vivo with Dermatophagoides pteronyssinus group 1 (Der p 1), and the expression of Iε-Cμ and Iε-Cγ circle transcripts was detected by using seminested PCR. Increased formation of eLTs with germinal center-like structures was discovered in patients with eosinophilic (20.69%) and noneosinophilic (17.31%) CRSwNP compared with that in patients with chronic rhinosinusitis without nasal polyps (5.66%) and control subjects (3.70%). The presence of eLTs was associated with increased expression of lymphorganogenic and inflammatory chemokines and cytokines, as well as their receptors. The expression of molecules required for immunoglobulin production, generation of follicular helper T cells, and production of IgE in eosinophilic polyps and IgG and IgA in both eosinophilic and noneosinophilic polyps were predominantly upregulated in patients with eLTs. After Der p 1 challenge ex vivo, Iε-Cμ transcript was detected only in eosinophilic polyps with eLTs but not in polyps without eLTs and noneosinophilic polyps. eLTs might support local immunoglobulin production and therefore significantly contribute to the development of CRSwNP. Copyright © 2017 American Academy of

  13. Prenatal and newborn immunoglobulin levels from mother-child pairs and risk of autism spectrum disorders

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    Lisa A. Croen

    2016-05-01

    Full Text Available Background. An etiological role for immune factors operating during early brain development in children with autism spectrum disorders (ASD has not yet been established. A major obstacle has been the lack of early biologic specimens that can be linked to later diagnosis. In a prior study, we found lower risk of ASD associated with higher levels of maternally-derived total IgG and Toxoplasmosis gondii (Toxo IgG in newborn blood spot specimens from children later diagnosed with ASD compared to population controls.Methods. We obtained maternal mid-gestational serum specimens and newborn screening blood spots from the California Genetics Disease Screening Program (GDSP for linked mother-baby pairs for 84 children with ASD and 49 children with developmental delay but not ASD (DD identified from California Department of Developmental Services records and for 159 population controls sampled from birth certificates. Immunoglobulin levels in maternal and newborn specimens were measured by solid phase immunoassays and analyzed in logistic regression models for total IgG, total IgM, and Toxo IgG, and, for maternal specimens only, Toxo IgM. Correlations between maternal and newborn ranked values were evaluated.Results. In both maternal and newborn specimens, we found significantly lower risk of ASD associated with higher levels of Toxo IgG. In addition, point estimates for all comparisons were <1.0 suggesting an overall pattern of lower immunoglobulin levels associated with higher ASD risk but most did not reach statistical significance. We did not find differences in maternal or newborn specimens comparing children with DD to controls. Discussion. These results are consistent with evidence from our prior study and other published reports indicating that immune factors during early neurodevelopment may be etiologically relevant to ASD. Lowered immunoglobulin levels may represent suboptimal function of the maternal immune system or reduced maternal exposure

  14. Molecular phylogeny of C1 inhibitor depicts two immunoglobulin-like domains fusion in fishes and ray-finned fishes specific intron insertion after separation from zebrafish

    International Nuclear Information System (INIS)

    Kumar, Abhishek; Bhandari, Anita; Sarde, Sandeep J.; Goswami, Chandan

    2014-01-01

    Highlights: • C1 inhibitors of fishes have two Ig domains fused in the N-terminal end. • Spliceosomal introns gain in two Ig domains of selected ray-finned fishes. • C1 inhibitors gene is maintained from 450 MY on the same locus. • C1 inhibitors gene is missing in frog and lampreys. • C1 inhibitors of tetrapod and fishes differ in the RCL region. - Abstract: C1 inhibitor (C1IN) is a multi-facet serine protease inhibitor in the plasma cascades, inhibiting several proteases, notably, regulates both complement and contact system activation. Despite huge advancements in the understanding of C1IN based on biochemical properties and its roles in the plasma cascades, the phylogenetic history of C1IN remains uncharacterized. To date, there is no comprehensive study illustrating the phylogenetic history of C1IN. Herein, we explored phylogenetic history of C1IN gene in vertebrates. Fishes have C1IN with two immunoglobulin like domains attached in the N-terminal region. The RCL regions of CIIN from fishes and tetrapod genomes have variations at the positions P2 and P1′. Gene structures of C1IN gene from selected ray-finned fishes varied in the Ig domain region with creation of novel intron splitting exon Im2 into Im2a and Im2b. This intron is limited to ray-finned fishes with genome size reduced below 1 Gb. Hence, we suggest that genome compaction and associated double-strand break repairs are behind this intron gain. This study reveals the evolutionary history of C1IN and confirmed that this gene remains the same locus for ∼450 MY in 52 vertebrates analysed, but it is not found in frogs and lampreys

  15. Molecular phylogeny of C1 inhibitor depicts two immunoglobulin-like domains fusion in fishes and ray-finned fishes specific intron insertion after separation from zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Abhishek, E-mail: akumar@bot.uni-kiel.de [Department of Genetics and Molecular Biology in Botany, Institute of Botany, Christian-Albrechts-University at Kiel, Kiel (Germany); Bhandari, Anita [Molecular Physiology, Zoological Institute, Christian-Albrechts-University at Kiel, Kiel (Germany); Sarde, Sandeep J. [Department of Genetics and Molecular Biology in Botany, Institute of Botany, Christian-Albrechts-University at Kiel, Kiel (Germany); Goswami, Chandan [National Institute of Science Education and Research, Bhubaneswar, Orissa (India)

    2014-07-18

    Highlights: • C1 inhibitors of fishes have two Ig domains fused in the N-terminal end. • Spliceosomal introns gain in two Ig domains of selected ray-finned fishes. • C1 inhibitors gene is maintained from 450 MY on the same locus. • C1 inhibitors gene is missing in frog and lampreys. • C1 inhibitors of tetrapod and fishes differ in the RCL region. - Abstract: C1 inhibitor (C1IN) is a multi-facet serine protease inhibitor in the plasma cascades, inhibiting several proteases, notably, regulates both complement and contact system activation. Despite huge advancements in the understanding of C1IN based on biochemical properties and its roles in the plasma cascades, the phylogenetic history of C1IN remains uncharacterized. To date, there is no comprehensive study illustrating the phylogenetic history of C1IN. Herein, we explored phylogenetic history of C1IN gene in vertebrates. Fishes have C1IN with two immunoglobulin like domains attached in the N-terminal region. The RCL regions of CIIN from fishes and tetrapod genomes have variations at the positions P2 and P1′. Gene structures of C1IN gene from selected ray-finned fishes varied in the Ig domain region with creation of novel intron splitting exon Im2 into Im2a and Im2b. This intron is limited to ray-finned fishes with genome size reduced below 1 Gb. Hence, we suggest that genome compaction and associated double-strand break repairs are behind this intron gain. This study reveals the evolutionary history of C1IN and confirmed that this gene remains the same locus for ∼450 MY in 52 vertebrates analysed, but it is not found in frogs and lampreys.

  16. [Prevalence of gene polymorphisms associated with immune-dependent diseases in the populations of North Eurasia].

    Science.gov (United States)

    Cherednichenko, A A; Trifonova, E A; Vagaitseva, K V; Bocharova, A V; Varzari, A M; Radzhabov, M O; Stepanov, V A

    2015-01-01

    The data on distribution of genetic diversity in gene polymorphisms associated with autoimmune and allergic diseases and with regulation of immunoglobulin E and cytokines levels in 26 populations of the Northern Eurasia is presented. Substantial correlation between the values of average expected heterozygosity by 44 gene polymorphisms with climatic and geographical factors has not been revealed. Clustering of population groups in correspondence with their geographic locations is observed. The degree of gene differentiation among populations and the selective neutrality of gene polymorphisms have been assessed. The results of our work evidence the substantial genetic diversity and differentiation of human populations by studied genes.

  17. An experience in the clinical use of specific immunoglobulin from horse blood serum for prophylaxis of Ebola haemorrhagic fever.

    Science.gov (United States)

    Borisevich, I V; Chemikova, Natalya K; Markov, V I; Krasnianskiy, V P; Borisevich, S V; Rozhdestvenskiy, E V

    The aim of this work was to estimate the efficacy and safety of single intramuscular introduction of specific heterologous immunoglobulin as prophylactic drug against Ebola hemorrhagic fever. Materials and methods. The specific heterologous immunoglobulin was introduced as a special prophylactic drug to 28 patients in epidemic situations, after skin hurt with infectious materials or contact with infectious blood. Clinico-laboratory observation was performed in 24 subjects after single intramuscular introduction of heterologous immunoglobulin Ebola. The samples of blood serum were investigated for immunoglobulin Ebola and antibodies to horse gamma-globulin on the 30th and 60th days after prophylaxis. Results. None of the subjects of the study contracted Ebola fever. There were no anaphylactic reactions after special prophylaxis with specific heterologous immunoglobulin. Among the subjects with normal allergic state 31% responded with local reactions; 13%, with a general reaction (mild case of the serum disease). Almost no reaction was observed in patients with unfavorable allergic state subjected to desensitizing therapy; in the absence of desensitizing therapy, 50% of patients with unfavorable allergic state exhibited local reactions; 17%, mild cases of the serum disease; 33%, moderate cases of the serum disease. In summary, if the tactics of immunoglobulin application was right, the quantity of local allergic reactions was 28%; of wide spread reactions, 6%. Weak serum disease was observed in 11% of the subjects. The prognostic period of resistance to Ebola fever was less than 30 days. Conclusion. The prophylactic use of specific immunoglobulin from horse blood serum against hemorrhagic Ebola fever is effective and relatively safe in patients subjected to desensitizing therapy.

  18. Oral Serum-Derived Bovine Immunoglobulin/Protein Isolate Has Immunomodulatory Effects on the Colon of Mice that Spontaneously Develop Colitis.

    Directory of Open Access Journals (Sweden)

    Anna Pérez-Bosque

    Full Text Available Dietary immunoglobulin concentrates prepared from animal plasma can modulate the immune response of gut-associated lymphoid tissue (GALT. Previous studies have revealed that supplementation with serum-derived bovine immunoglobulin/protein isolate (SBI ameliorates colonic barrier alterations in the mdr1a-/- genetic mouse model of IBD. Here, we examine the effects of SBI on mucosal inflammation in mdr1a-/- mice that spontaneously develop colitis. Wild type (WT mice and mice lacking the mdr1a gene (KO were fed diets supplemented with either SBI (2% w/w or milk proteins (Control diet, from day 21 (weaning until day 56. Leucocytes in mesenteric lymph nodes (MLN and in lamina propria were determined, as was mucosal cytokine production. Neutrophil recruitment and activation in MLN and lamina propria of KO mice were increased, but were significantly reduced in both by SBI supplementation (p < 0.05. The increased neutrophil recruitment and activation observed in KO mice correlated with increased colon oxidative stress (p < 0.05 and SBI supplementation reduced this variable (p < 0.05. The Tact/Treg lymphocyte ratios in MLN and lamina propria were also increased in KO animals, but SBI prevented these changes (both p < 0.05. In the colon of KO mice, there was an increased production of mucosal pro-inflammatory cytokines such as IL-2 (2-fold, IL-6 (26-fold and IL-17 (19-fold, and of chemokines MIP-1β (4.5-fold and MCP-1 (7.2-fold. These effects were significantly prevented by SBI (p < 0.05. SBI also significantly increased TGF-β secretion in the colon mucosa, suggesting a role of this anti-inflammatory cytokine in the modulation of GALT and the reduction of the severity of the inflammatory response during the onset of colitis.

  19. Next-generation sequencing technology a new tool for killer cell immunoglobulin-like receptor allele typing in hematopoietic stem cell transplantation.

    Science.gov (United States)

    Maniangou, B; Retière, C; Gagne, K

    2018-02-01

    Killer cell Immunoglobulin-like Receptor (KIR) genes are a family of genes located together within the leukocyte receptor cluster on human chromosome 19q13.4. To date, 17 KIR genes have been identified including nine inhibitory genes (2DL1/L2/L3/L4/L5A/L5B, 3DL1/L2/L3), six activating genes (2DS1/S2/S3/S4/S5, 3DS1) and two pseudogenes (2DP1, 3DP1) classified into group A (KIR A) and group B (KIR B) haplotypes. The number and the nature of KIR genes vary between the individuals. In addition, these KIR genes are known to be polymorphic at allelic level (907 alleles described in July 2017). KIR genes encode for receptors which are predominantly expressed by Natural Killer (NK) cells. KIR receptors recognize HLA class I molecules and are able to kill residual recipient leukemia cells, and thus reduce the likelihood of relapse. KIR alleles of Hematopoietic Stem Cell (HSC) donor would require to be known (Alicata et al. Eur J Immunol 2016) because the KIR allele polymorphism may affect both the KIR + NK cell phenotype and function (Gagne et al. Eur J Immunol 2013; Bari R, et al. Sci Rep 2016) as well as HSCT outcome (Boudreau et al. JCO 2017). The introduction of the Next Generation Sequencing (NGS) has overcome current conventional DNA sequencing method limitations, known to be time consuming. Recently, a novel NGS KIR allele typing approach of all KIR genes was developed by our team in Nantes from 30 reference DNAs (Maniangou et al. Front in Immunol 2017). This NGS KIR allele typing approach is simple, fast, reliable, specific and showed a concordance rate of 95% for centromeric and telomeric KIR genes in comparison with high-resolution KIR typing obtained to those published data using exome capture (Norman PJ et al. Am J Hum Genet 2016). This NGS KIR allele typing approach may also be used in reproduction and to better study KIR + NK cell implication in the control of viral infections. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Preparation of γ-immunoglobulins coupled with DTPA and their labelling with trivalent metal radionuclides for radiotherapy

    International Nuclear Information System (INIS)

    Rekova, M.; Miler, V.; Budsky, F.; Malek, Z.; Prokop, J.; Prazak, Z.

    2007-06-01

    The scope of the report is as follows: immunoglobulin coupling with cDTPAA and labelling of the conjugate with 90 Y; Acid-base and complexation equilibria in the coupled immunoglobulin solution; Theory of the complex equilibrium of yttrium between coupled immunoglobulin and EDTA; and Procedures and results of recent experiments. The following was achieved: (i) The dependence of the bovine immunoglobulin on the cDTPAA/IgG coupling ratio and immunoglobulin concentration was obtained; (ii) A procedure aimed to free phosphate buffer from ubiquitous trivalent cations was tested; (iii) The procedure of lyophilization of coupled bovine IgG-DTPA in a phosphate buffer at pH 7.34 and I = 0.16 mol.l -1 .was elaborated. (iv) A procedure for lyophilization of the coupled CD20 monoclonal antibody in the same phosphate buffer was elaborated. (v) Acid-base and complexation equilibria were calculated for citrate and phosphate buffer solutions in the presence of coupled immunoglobulin. ( vi) A theory of the complexation equilibrium of yttrium between coupled immunoglobulin and EDTA was developed. (vii) Experiments were performed leading to the determination of a so far unknown constant of complexity of yttrium to DTPA coupled to immunoglobulin; its 3rd and 4th dissociation constants. (viii) The method sub (vii) can be applied to the determination of the complexity constants of other radionuclides with DTPA coupled to immunoglobulin; the 3rd and 4th dissociation constants of IgG-DTPA will not have to be sought any more. (ix) Samples of lyophilizate of the Y-CD20-DTPA complex can be sent to the biochemical laboratory for immunoreactivity determination. (x) Lyophilizates from experiments (iv-vi) are stored in a refrigerator at 4 deg C to be used for labelling with 177 Lu. (xi) The results obtained can be used to plan an experiment with CD20 in which a specific radioactivity of 400 MBq 177 Lu per mg CD20 will be achieved. (P.A.)

  1. Inhibition mechanisms of hemoglobin, immunoglobulin G, and whole blood in digital and real-time PCR.

    Science.gov (United States)

    Sidstedt, Maja; Hedman, Johannes; Romsos, Erica L; Waitara, Leticia; Wadsö, Lars; Steffen, Carolyn R; Vallone, Peter M; Rådström, Peter

    2018-04-01

    Blood samples are widely used for PCR-based DNA analysis in fields such as diagnosis of infectious diseases, cancer diagnostics, and forensic genetics. In this study, the mechanisms behind blood-induced PCR inhibition were evaluated by use of whole blood as well as known PCR-inhibitory molecules in both digital PCR and real-time PCR. Also, electrophoretic mobility shift assay was applied to investigate interactions between inhibitory proteins and DNA, and isothermal titration calorimetry was used to directly measure effects on DNA polymerase activity. Whole blood caused a decrease in the number of positive digital PCR reactions, lowered amplification efficiency, and caused severe quenching of the fluorescence of the passive reference dye 6-carboxy-X-rhodamine as well as the double-stranded DNA binding dye EvaGreen. Immunoglobulin G was found to bind to single-stranded genomic DNA, leading to increased quantification cycle values. Hemoglobin affected the DNA polymerase activity and thus lowered the amplification efficiency. Hemoglobin and hematin were shown to be the molecules in blood responsible for the fluorescence quenching. In conclusion, hemoglobin and immunoglobulin G are the two major PCR inhibitors in blood, where the first affects amplification through a direct effect on the DNA polymerase activity and quenches the fluorescence of free dye molecules, and the latter binds to single-stranded genomic DNA, hindering DNA polymerization in the first few PCR cycles. Graphical abstract PCR inhibition mechanisms of hemoglobin and immunoglobulin G (IgG). Cq quantification cycle, dsDNA double-stranded DNA, ssDNA single-stranded DNA.

  2. Family analysis of immunoglobulin classes and subclasses in children with autistic disorder.

    Science.gov (United States)

    Spiroski, Mirko; Trajkovski, Vladimir; Trajkov, Dejan; Petlichkovski, Aleksandar; Efinska-Mladenovska, Olivija; Hristomanova, Slavica; Djulejic, Eli; Paneva, Meri; Bozhikov, Jadranka

    2009-11-01

    Autistic disorder is a severe neurodevelopment disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviours and interests. There are strong lines of evidence to suggest that the immune system plays an important role in the pathogenesis of autistic disorder. The aim of this study was to analyze quantitative plasma concentration of immunoglobulin classes, and subclasses in autistic patients and their families. The investigation was performed retrospectively in 50 persons with autistic disorder in the Republic of Macedonia. Infantile autistic disorder was diagnosed by DSM-IV and ICD-10 criteria. Plasma immunoglobulin classes (IgM, IgA, and IgG) and subclasses (IgG1, IgG2, IgG3, and IgG4) were determined using Nephelometer Analyzer BN-100. Multiple comparisons for the IgA variable have shown statistically significant differences between three pairs: male autistic from the fathers (p = 0,001), female autistic from the mothers (p = 0,008), as well as healthy sisters from the fathers (p = 0,011). Statistically significant differences found between three groups regarding autistic disorder (person with autistic disorder, father/mother of a person with autistic disorder, and brother/sister) independent of sex belongs to IgA, IgG2, and IgG3 variables. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations.

  3. Diverse binding site structures revealed in homology models of polyreactive immunoglobulins

    Science.gov (United States)

    Ramsland, Paul A.; Guddat, Luke W.; Edmundson, Allen B.; Raison, Robert L.

    1997-09-01

    We describe here computer-assisted homology models of the combiningsite structure of three polyreactive immunoglobulins. Template-based modelsof Fv (VL-VH) fragments were derived forthe surface IgM expressed by the malignant CD5 positive B cells from threepatients with chronic lymphocytic leukaemia (CLL). The conserved frameworkregions were constructed using crystal coordinates taken from highlyhomologous human variable domain structures (Pot and Hil). Complementaritydetermining regions (CDRs) were predicted by grafting loops, taken fromknown immunoglobulin structures, onto the Fv framework models. The CDRtemplates were chosen, where possible, to be of the same length and of highresidue identity or similarity. LCDR1, 2 and 3 as well as HCDR1 and 2 forthe Fv were constructed using this strategy. For HCDR3 prediction, adatabase containing the Cartesian coordinates of 30 of these loops wascompiled from unliganded antibody X-ray crystallographic structures and anHCDR3 of the same length as that of the B CLL Fv was selected as a template.In one case (Yar), the resulting HCDR3 model gave unfavourable interactionswhen incorporated into the Fv model. This HCDR3 was therefore modelled usingan alternative strategy of construction of the loop stems, using apreviously described HCDR3 conformation (Pot), followed by chain closurewith a β-turn. The template models were subjected to positionalrefinement using energy minimisation and molecular dynamics simulations(X-PLOR). An electrostatic surface description (GRASP) did not reveal acommon structural feature within the binding sites of the three polyreactiveFv. Thus, polyreactive immunoglobulins may recognise similar and multipleantigens through a diverse array of binding site structures.

  4. Variations in riboflavin binding by human plasma: identification of immunoglobulins as the major proteins responsible

    International Nuclear Information System (INIS)

    Innis, W.S.; McCormick, D.B.; Merrill, A.H. Jr.

    1985-01-01

    Riboflavin binding by plasma proteins from healthy human subjects was examined by equilibrium dialysis using a physiological concentration of [2-14C]riboflavin (0.04 microM). Binding ranged from 0.080 to 0.917 pmole of riboflavin/mg of protein (with a mean +/- SD of 0.274 +/- 0.206), which corresponded to 4.14 to 49.4 pmole/ml of plasma (15.5 +/- 11.0) (N = 34). Males and females yielded similar results. Upon fractionation of plasma by gel filtration, the major riboflavin-binding components eluted with albumin and gamma-globulins. Albumin was purified and found to bind riboflavin only very weakly (Kd = 3.8 to 10.4 mM), although FMN and photochemical degradation products (e.g., lumiflavine and lumichrome) were more tightly bound. Binding in the gamma-globulin fraction was attributed to IgG and IGA because the binding protein(s) and immunoglobulins copurified using various methods were removed by treatment of plasma with protein A-agarose, and were coincident upon immunoelectrophoresis followed by autoradiography to detect [2-14C]riboflavin. Differences among the plasma samples correlated with the binding recovered with the immunoglobulins. Binding was not directly related to the total IgG or IgA levels of subjects. Hence, it appears that the binding is due to a subfraction of these proteins. These findings suggest that riboflavin-binding immunoglobulins are a major cause of variations in riboflavin binding in human circulation, and may therefore affect the utilization of this micronutrient

  5. Salivary immunoglobulin classes in Nigerian cigarette smokers: Indication for increased risk of oral diseases.

    Science.gov (United States)

    Olayanju, Ayodeji Olatunde; Rahamon, Sheu Kadiri; Arinola, Olatunbosun Ganiyu

    2012-09-01

    Cigarette smoking is a worldwide social epidemic and it is one of the main causes of preventable death and disability. Gingivitis, periodontitis, pocket depth, attachment loss, alveolar bone loss, and tooth loss are some of oral pathologies commonly found in cigarette smokers. The aim of this study was to explore, for the first time among Nigerians, the interplay between components of cigarette smoke and salivary levels of immunoglobulin classes so as to provide oral immunological based reasons for oral diseases in cigarette smokers. In this case-control study, 5 mL of unstimulated saliva was collected in plain sample bottles from 24 active smokers who smoke at least 6 sticks of cigarette per day and 21 sex and age-matched non-smokers who were apparently healthy. The samples were spun and supernatant stored at -20°C until assayed. The immunoglobulin levels of the samples were estimated using enzyme-linked immunosorbent assay (ELISA). Student's t-test (unpaired) was used to determine significant differences between the two groups. P values less than 0.05 was considered significant. No significant differences were observed in the mean salivary levels of IgG, IgA, and IgE. Only IgM was significantly lower in smokers compared with non-smokers (P = 0.038). The proportion of smokers with detectable level of salivary IgE was lower compared with controls. Our study showed that there is decreased salivary IgM in smokers. This observation suggests that reduced salivary immunoglobulin level of IgM might be involved in the pathogenesis of oral diseases in cigarette smokers.

  6. Family Analysis of Immunoglobulin Classes and Subclasses in Children with Autistic Disorder

    Directory of Open Access Journals (Sweden)

    Mirko Spiroski

    2009-11-01

    Full Text Available Autistic disorder is a severe neurodevelopment disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviours and interests. There are strong lines of evidence to suggest that the immune system plays an important role in the pathogenesis of autistic disorder. The aim of this study was to analyze quantitative plasma concentration of immunoglobulin classes, and subclasses in autistic patients and their families. The investigation was performed retrospectively in 50 persons with autistic disorder in the Republic of Macedonia. Infantile autistic disorder was diagnosed by DSM-IV and ICD-10 criteria. Plasma immunoglobulin classes (IgM, IgA, and IgG and subclasses (IgG1, IgG2, IgG3, and IgG4 were determined using Nephelometer Analyzer BN-100. Multiple comparisons for the IgA variable have shown statistically significant differences between three pairs: male autistic from the fathers (p = 0,001, female autistic from the mothers (p = 0,008, as well as healthy sisters from the fathers (p = 0,011. Statistically significant differences found between three groups regarding autistic disorder (person with autistic disorder, father/mother of a person with autistic disorder, and brother/sister independent of sex belongs to IgA, IgG2, and IgG3 variables. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p < 0,001, and healthy brothers and sisters from the fathers and mothers (p < 0,001. Comparison between healthy children and children with autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations.

  7. Early Bronchus-Associated Lymphoid Tissue Lymphoma Diagnosed with Immunoglobulin Heavy Chain Molecular Testing

    Directory of Open Access Journals (Sweden)

    Pen Li

    2016-01-01

    Full Text Available When extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT, a low grade B-cell lymphoma, arises in the lung it is referred to as bronchus-associated lymphoid tissue (BALT lymphoma. We describe a patient with a history of Sjögren’s syndrome and rheumatoid arthritis with dyspnea and imaging consistent with lymphoid interstitial pneumonia (LIP. However, while histology and immunohistochemistry lacked definitive features of a lymphoma, immunoglobulin heavy chain (IgH polymerase chain reaction testing demonstrated B-cell monoclonality, consistent with an early BALT lymphoma.

  8. Intravenous Immunoglobulin Monotherapy for Granulomatous Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency.

    Science.gov (United States)

    Hasegawa, Mizue; Sakai, Fumikazu; Okabayashi, Asako; Sato, Akitoshi; Yokohori, Naoko; Katsura, Hideki; Asano, Chihiro; Kamata, Toshiko; Koh, Eitetsu; Sekine, Yasuo; Hiroshima, Kenzo; Ogura, Takashi; Takemura, Tamiko

    2017-11-01

    Common variable immunodeficiency (CVID) is a heterogeneous subset of immunodeficiency disorders. Recurrent bacterial infection is the main feature of CVID, but various non-infectious complications can occur. A 42-year-old woman presented with cough and abnormal chest X-ray shadows. Laboratory tests showed remarkable hypogammaglobulinemia. Computed tomography revealed multiple consolidation and nodules on the bilateral lung fields, systemic lymphadenopathy, and splenomegaly. A surgical lung biopsy specimen provided the final diagnosis of lymphoproliferative disease in CVID, which was grouped under the term granulomatous lymphocytic interstitial lung disease. Interestingly, the lung lesions of this case resolved immediately after the initiation of intravenous immunoglobulin monotherapy.

  9. Small bowel obstruction caused by peritoneal immunoglobulin G4-related disease mimicking carcinomators: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Coulier, Bruno; Montfort, Luc; Pierard, Frederic [Clinique St. Luc, Bouge (Belgium); Beniuga, Gabrique; Gielen, Lsabelle [Institute of Pathology and Genetics, Gosselies (Belgium)

    2014-02-15

    We hereby report a case of diffuse pelvic peritoneal involvement by immunoglobulin G4-related disease (IgG4-RD). Numerous pelvic masses and nodules showing delayed enhancement on enhanced abdominal CT were found to congregate in the pelvic organs of a 57-year-old female presenting with intestinal subocclusion. The differentiation between peritoneal IgG4-RD and pelvic peritoneal carcinomatosis was only made by histopathology and immunohistochemistry performed after surgical resection. Autoimmune pancreatitis represents the historical prototype of IgG4-RD, but the spectrum of manifestations involving various organs has expanded during the last decade. In this report, we shortly review this clinical entity.

  10. Immunoglobulin M and G antibody responses to Plasmodium falciparum glutamate-rich protein

    DEFF Research Database (Denmark)

    Dziegiel, Morten Hanefeld; Rowe, P; Bennett, S

    1993-01-01

    were measured with a recombinant fusion protein consisting of the carboxy-terminal 783 amino acids of the GLURP. Samples for the study were obtained during a longitudinal malaria morbidity survey performed in The Gambia; cross-sectional surveys were performed at the beginning of the transmission season......The aims of the present study were to describe the age-related immunoglobulin M (IgM) and IgG response to part of a 220-kDa glutamate-rich protein (GLURP) from Plasmodium falciparum and to determine possible correlations of possession of these antibodies with malaria morbidity. IgM and IgG levels...

  11. Early changes of lymphocyte RNA and serum immunoglobulins following chronic exposure to benzene

    Energy Technology Data Exchange (ETDEWEB)

    Chircu, V.; Ionescu, M.; Zgoan

    Hematologic and immunochemical investigations carried out in 270 workers with chronic exposure to benzene demonstrated changes of the nucleologram and of the area of lymphocyte nucleoli as well as disorders of the humoral immune response revealed by radial immunodiffusion. The numerical rise of bi- and polynucleolated cells, of cells with irregular macronucleoli as well as an enlargement of the nucleolar area are assumed to reflect an increase of the endolymphocytic amounts of RNA. An increased capacity of immunoglobulin formation, particularly of IgM, was also observed. All these changes are considered as early signs of an enhanced immune reactivity following chronic exposure to benzene.

  12. Quantification of equine immunoglobulin A in serum and secretions by a fluorescent bead-based assay.

    Science.gov (United States)

    Schnabel, Christiane L; Babasyan, Susanna; Freer, Heather; Wagner, Bettina

    2017-06-01

    Only few quantitative reports exist about the concentrations and induction of immunoglobulin A (IgA) in mucosal secretions of horses. Despite this, it is widely assumed that IgA is the predominant immunoglobulin on mucosal surfaces in the horse. Here, two new monoclonal antibodies (mAbs) against equine IgA, clones 84-1 and 161-1, were developed and characterized in detail. Both IgA mAbs specifically bound monomeric and dimeric equine IgA in different applications, such as Western blots and fluorescent bead-based assays. Cross-reactivity with other equine immunoglobulin isotypes was not observed. The new IgA mAb 84-1 was used in combination with the previously characterized anti-equine IgA mAb BVS2 for the development and validation of a fluorescent bead-based assay to quantify total IgA in equine serum and various secretions. The IgA assay's linear detection ranged from 64pg/ml to 1000ng/ml. For the quantification of IgA in serum or in secretions an IgA standard was purified from serum or nasal wash fluid (secretory IgA), respectively. The different standards were needed for accurate IgA quantification in the respective samples taking the different signal intensities of monomeric and dimeric IgA on the florescent bead-based assay into account. IgA was quantified by the bead-based assay established here in different equine samples of healthy adult individuals. In serum the median total IgA was 0.45mg/ml for Thoroughbred horses (TB, n=10) and 1.16mg/ml in Icelandic horses (ICH, n=12). In nasopharyngeal secretions of TB (n=7) 0.13mg/ml median total IgA was measured, and 0.25mg/ml for ICH (n=12). Saliva of ICH (n=6) contained a median of 0.15mg/ml, colostrum of Warmbloods (n=8) a median of 1.89mg/ml IgA. Compared to IgG1 and IgG4/7 quantified in the same samples, IgA appeared as the major immunoglobulin isotype in nasopharyngeal secretions and saliva while it is a minor isotype in serum and colostrum. The newly developed monoclonal antibodies against equine IgA and the

  13. Application of perturbed angular correlation spectroscopy in IgG immunoglobulins

    International Nuclear Information System (INIS)

    Silva, A.S.; Amaral, A.A.; Lapolli, A.L.; Carbonari, A.W.

    2009-01-01

    In the present work, the technique of perturbed angular correlation (PAC) spectroscopy was used to measure the electric hyperfine field at IgG immunoglobulins using 111 In → 111 Cd and 181 Hf → 181 Ta probe nuclei. The biological materials studied in this work were originating from the immunological response of different mice lineages infected by the Y strain of T. cruzi. The samples were measured at room temperature (295K) and at liquid nitrogen temperature (77K). The PAC results showed that, samples measured with 111 In obtained better results when they were compared with samples measured with 181 Hf. (author)

  14. Mouse myeloma cells that make short immunoglobulin heavy chains: pleiotropic effects on glycosylation and chain assembly

    OpenAIRE

    1984-01-01

    Two variants in immunoglobulin heavy chain production, derived from the MPC 11 mouse myeloma cell line, make short heavy (H) chains with identical precise deletions of the CH3 domain. The CH3 domain is expressed in the H chain mRNA from both variants. Although in vitro translation of this mRNA produces one H chain species, deleted heavy chains are secreted as heavy-light (HL) and H2L2 moieties in contrast to MPC 11, which secretes only H2L2 . The heavy chains of HL apparently contain more car...

  15. Application of perturbed angular correlation spectroscopy in IgG immunoglobulins

    Energy Technology Data Exchange (ETDEWEB)

    Silva, A.S.; Amaral, A.A.; Lapolli, A.L.; Carbonari, A.W. [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil)], e-mail: asilva@usp.br

    2009-07-01

    In the present work, the technique of perturbed angular correlation (PAC) spectroscopy was used to measure the electric hyperfine field at IgG immunoglobulins using {sup 111}In {yields}{sup 111}Cd and {sup 181}Hf {yields} {sup 181}Ta probe nuclei. The biological materials studied in this work were originating from the immunological response of different mice lineages infected by the Y strain of T. cruzi. The samples were measured at room temperature (295K) and at liquid nitrogen temperature (77K). The PAC results showed that, samples measured with {sup 111}In obtained better results when they were compared with samples measured with {sup 181}Hf. (author)

  16. Use of (/sup 75/Se)selenomethionine in immunoglobulin biosynthetic studies

    Energy Technology Data Exchange (ETDEWEB)

    Gutman, G A; Warner, N L; Harris, A W; Bowles, A [Walter and Elisa Hall Institute of Medical Research, Victoria (Australia). Genetics Unit; Royal Melbourne Hospital, Victoria (Australia))

    1978-05-01

    The gamma-emitting amino acid analog, (/sup 75/Se) selenomethionine, has been used as a biosynthetic label for immunoglobulins secreted by plasmacytomas in tissue culture. The secreted products are structurally intact with respect to their antibody combining sites and their class and allotype antigenic specificities. A component of (/sup 75/Se) selenomethionine preparations was found to bind to fetal calf serum proteins, in a manner releasable by mercaptoethanol, but not by sodium dodecyl sulfate and urea. Methods for circumventing the problems caused by this binding are described.

  17. A case of immunoglobulin G-4 related sclerosing disease mimicking lung cancer

    International Nuclear Information System (INIS)

    Kwon, Soo Hee; Lee, Young Kyung; Shim, Mi Suk; Lee, Hyang Im

    2013-01-01

    Immunoglobulin (Ig) G4-related sclerosing disease is a recently described systemic fibro-inflammatory disease associated with an elevated circulating level of IgG4 and extensive IgG4-positive lymphoplasmacytic infiltration, resulting in sclerosing inflammation involving various body organs. We experienced one case where surgery confirmed IgG4-related sclerosing disease as a solitary lung mass mimicking lung cancer. We report radiologic findings including chest computed tomography and positron emission tomography computed tomography, with clinical manifestations of IgG4-related sclerosing disease.

  18. Immunoglobulin G4-Related Sclerosing Disease Involving the Urethra: Case Report

    International Nuclear Information System (INIS)

    Choi, Jin Woo; KIm, Sang Youn; Cho, Jeong Yeon; Kim, Seung Hyup; Moon, Kyung Chul

    2012-01-01

    Immunoglobulin G4 (IgG4)-related sclerosing disease is a systemic disease characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration in various organs. We described the imaging findings of an IgG4-related inflammatory pseudotumor in the urethra. The urethral mass showed isoattenuation on unenhanced CT images, delayed enhancement on enhanced CT images, iso- to slight hyper-intensity on T1 and T2 weighted magnetic resonance images, diffusion restriction on diffusion weighted images, and heterogeneously low echogeneity on ultrasonography.

  19. The application of PET/CT in immunoglobulin G4-related disease

    International Nuclear Information System (INIS)

    Zhang Huiwei; Zhao Jun

    2013-01-01

    Immunoglobulin G4 (IgG4)-related disease is a kind of new systemic entity characterized by mass-forming lesions in various organs that consist of lymphoplasmacytic infiltrates and fibrosclerosis with numerous IgG4-positive plasma cells. PET/CT has been widely used in clinical as a whole body examination that earned plenty of successful experience, especially in multiple locations and organs cancer such as lymphoma. PET/CT also has a potential application in IgG4-related diseases as its feature of systemic. (authors)

  20. Appendiceal immunoglobulin G4-related disease mimicking appendiceal tumor or appendicitis: A case report

    International Nuclear Information System (INIS)

    Kim, Hyun Soo; Kang, Won Kyung; Chung, Dong Jin

    2016-01-01

    Immunoglobulin G4 (IgG4)-related disease is an autoimmune disease that forms tumorous lesions. Several cases involving various organs are reported, however, IgG4-related disease involving appendix has not been reported yet. In this report, we presented a case of IgG4-related disease of appendix, which raised a suspicion of appendiceal tumor or usual appendicitis and, therefore, led to unnecessary surgical resection. IgG4-related disease should be considered in the differential diagnosis for a mass-like swelling of the appendix, in order to avoid unnecessary surgery

  1. Small bowel obstruction caused by peritoneal immunoglobulin G4-related disease mimicking carcinomators: Case report

    International Nuclear Information System (INIS)

    Coulier, Bruno; Montfort, Luc; Pierard, Frederic; Beniuga, Gabrique; Gielen, Lsabelle

    2014-01-01

    We hereby report a case of diffuse pelvic peritoneal involvement by immunoglobulin G4-related disease (IgG4-RD). Numerous pelvic masses and nodules showing delayed enhancement on enhanced abdominal CT were found to congregate in the pelvic organs of a 57-year-old female presenting with intestinal subocclusion. The differentiation between peritoneal IgG4-RD and pelvic peritoneal carcinomatosis was only made by histopathology and immunohistochemistry performed after surgical resection. Autoimmune pancreatitis represents the historical prototype of IgG4-RD, but the spectrum of manifestations involving various organs has expanded during the last decade. In this report, we shortly review this clinical entity.

  2. Tumefactive immunoglobulin G4-related disease involving the dura mater: A case report and literature review

    International Nuclear Information System (INIS)

    Lee, Jeong Hoon; Lee, Ji Hoon; Ko, Yong; Paik, Seoung Sam; Lee, Young Jun; Park, Dong Woo

    2015-01-01

    Immunoglobulin G4 (IgG4)-related disease is a well-known disorder characterized by an inflammatory reaction with an increase in the number of IgG4-positive plasma cells associated with sclerosis. IgG4-related disease often affects the dura mater with a pattern of diffuse thickening when the central nervous system is involved. However, some nodular dural thickening requires discrimination from tumors because of obviously different treatment options. We report of a case of IgG4-related disease with tumefactive dural involvement

  3. Plasma exchange in Immunoglobulin A nephropathy with thrombotic microangiopathy and acute cortical necrosis

    Directory of Open Access Journals (Sweden)

    P Doddi

    2016-01-01

    Full Text Available A 25-year-old female presented with decreased urine output, deranged renal function, thrombocytopenia, and hemolytic anemia. Kidney biopsy was consistent with thrombotic microangiopathy with acute cortical necrosis and Immunoglobulin A nephropathy (IgAN. Hemolytic anemia, thrombocytopenia and urine output improved after five sessions of plasma exchange. Renal function showed a delayed recovery and serum creatinine normalized by 3 months. This is first case of successful use of plasma exchange in hemolytic uremic syndrome with cortical necrosis associated with IgAN.

  4. Clinical applications of immunoglobulin in neuromuscular diseases: focus on inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    Paulo Victor Sgobbi de Souza

    2014-12-01

    Full Text Available During recent years, an increasing number of neuromuscular diseases have been recognized either to be caused primarily by autoimmune mechanisms, or to have important autoimmune components. The involved pathophysiological mechanisms and clinical manifestations have been better recognized and many of these disorders are potentially treatable by immunosuppression or by immunomodulation with intravenous immunoglobulin (IVIg. IVIg has been tried in a variety of immune-mediated neurological diseases, being target of widespread use in central and peripheral nervous systems diseases. Objective To give an overview of the main topics regarding the mechanism of action and different therapeutic uses of IVIg in neurological practice, mainly in neuromuscular diseases.

  5. Thymocyte plasma membrane of the rainbow trout, Salmo gairdneri: Associated immunoglobulin and heteroantigens

    Science.gov (United States)

    Warr, G.W.; DeLuca, D.; Anderson, D.P.

    1983-01-01

    1. Thymic lymphocytes of the rainbow trout, S. gairdneri were disrupted and a plasma membrane containing fraction isolated by differential and buoyant density centrifugation.2. Radioiodine introduced into the membrane by the lactoperoxidase catalyzed reaction and immunoglobulin (identified by radioimmunoassay with monoclonal antibody) both copurified in the plasma membrane fraction.3. Rabbit antibody raised to the plasma membrane fraction showed a strong reaction with trout lymphocytes in immunofluorescence, was mitogenic for trout lymphocytes, and recognized lymphocyte membrane heteroantigens of molecular weight > 70,000 in the thymus and 45,000–95,000 in the head kidney.

  6. The second immunoglobulin class is commonly present in cartilaginous fish belonging to the order Rajiformes.

    Science.gov (United States)

    Kobayashi, K; Tomonaga, S

    1988-02-01

    Six species of cartilaginous fish distributed into four orders, Rajiformes (skates and guitarfishes), Myliobatiformes (rays), Heterodontiformes (sharks) and Carcharhiniformes (sharks), were investigated for the possible presence of a second class of immunoglobulin (Ig) other than IgM. Among those orders, fish belonging to the order Rajiformes were found to have a second Ig (IgR) with a non-covalently associated dimeric structure in which the H chain was different from that of IgM in mol. wt and antigenicity. Cartilaginous fish belonging to the other orders investigated had only one class of IgM.

  7. [Adult-onset Still's disease with pulmonary and cardiac involvement and response to intravenous immunoglobulin].

    Science.gov (United States)

    Neto, Nilton Salles Rosa; Waldrich, Leandro; de Carvalho, Jozélio Freire; Pereira, Rosa Maria Rodrigues

    2009-01-01

    Cardiopulmonary manifestations of adult-onset Still's disease (AOSD) include pericarditis, pleural effusion, transient pulmonary infiltrates, pulmonary interstitial disease and myocarditis. Serositis are common but pneumonitis and myocarditis are not and bring elevated risk of mortality. They may manifest on disease onset or flares. Previously reported cases were treated with high-dose glucocorticoids and immunosupressants and, when refractory, intravenous immunoglobulin (IVIG). We report an AOSD patient whose flare presented with severe pleupneumonitis and myopericarditis and, following nonresponse to a methylprednisolone pulse, high dose of prednisone and cyclosporine A, recovered after a 2-day 1g/kg/day IVIG infusion.

  8. Influence of elevated body temperature on circulating immunoglobulin-secreting cells

    DEFF Research Database (Denmark)

    Kappel, M; Barington, T; Gyhrs, A

    1995-01-01

    This work was designed to investigate the effect of in vivo hyperthermia in man on circulating immunoglobulin-secreting cells. Eight healthy male volunteers were immersed into a hot waterbath (WI) (water temperature 39.5 degrees C) for 2 h, whereby their body temperature rose to 39.5 degrees C....... On another occasion they served as their own controls, being immersed into thermoneutral water (water temperature 34.5 degrees C) for 2 h. Blood samples were drawn before immersion, at body temperatures of 38, 39 and 39.5 degrees C, as well as 2 h after WI when their body temperatures were normalized...

  9. Appendiceal immunoglobulin G4-related disease mimicking appendiceal tumor or appendicitis: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Soo; Kang, Won Kyung; Chung, Dong Jin [Yeouido St. Mary' s Hospital, The Catholic University of Korea, Seoul (Korea, Republic of)

    2016-02-15

    Immunoglobulin G4 (IgG4)-related disease is an autoimmune disease that forms tumorous lesions. Several cases involving various organs are reported, however, IgG4-related disease involving appendix has not been reported yet. In this report, we presented a case of IgG4-related disease of appendix, which raised a suspicion of appendiceal tumor or usual appendicitis and, therefore, led to unnecessary surgical resection. IgG4-related disease should be considered in the differential diagnosis for a mass-like swelling of the appendix, in order to avoid unnecessary surgery.

  10. Purified natural pig immunoglobulins can substitute dietary zinc in reducing piglet post weaning diarrhoea

    DEFF Research Database (Denmark)

    Hedegaard, Chris Juul; Lauridsen, Charlotte; Heegaard, Peter M. H.

    2017-01-01

    antibiotic resistance and pose environmental problems. Recently, in an experimental model of PWD, we observed that oral administration of purified porcine immunoglobulin G (ppIgG) from pooled natural pig plasma could reduce enteric infection. In the present study we were able to reproduce these results...... as it was observed that oral ppIgG accelerated clearance of faecal haemolytic bacteria in pigs challenged with E. coli in comparison with pigs not receiving ppIgG. This effect was observed upon feeding ppIgG for seven days postweaning suggesting that ppIgG does not have to be used prophylactically for several days...

  11. Role of defective Oct-2 and OCA-B expression in immunoglobulin production and Kaposi's sarcoma-associated herpesvirus lytic reactivation in primary effusion lymphoma.

    Science.gov (United States)

    Di Bartolo, Daniel L; Hyjek, Elizabeth; Keller, Shannon; Guasparri, Ilaria; Deng, Hongyu; Sun, Ren; Chadburn, Amy; Knowles, Daniel M; Cesarman, Ethel

    2009-05-01

    Primary effusion lymphoma (PEL) is a distinct type of B-cell non-Hodgkin lymphoma characterized by the presence of Kaposi's sarcoma-associated herpesvirus (KSHV/human herpesvirus 8). Despite having a genotype and gene expression signature of highly differentiated B cells, PEL does not usually express surface or cytoplasmic immunoglobulin (Ig). We show the lack of Oct-2 and OCA-B transcription factors to be responsible, at least in part, for this defect in Ig production. Like Ig genes, ORF50, the key regulator of the switch from latency to lytic reactivation, contains an octamer motif within its promoter. We therefore examined the impact of Oct-2 and OCA-B on ORF50 activation. The binding of Oct-1 to the ORF50 promoter has been shown to significantly enhance ORF50 transactivation. We found that Oct-2, on the other hand, inhibited ORF50 expression and consequently lytic reactivation by competing with Oct-1 for the octamer motif in the ORF50 promoter. Our data suggest that Oct-2 downregulation in infected cells would be favorable to KSHV in allowing for efficient viral reactivation.

  12. Investigation of T-cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) polymorphisms in essential thrombocythaemia (ET).

    Science.gov (United States)

    Han, Fuyan; Wang, Guanghai; Li, Yuantang; Tian, Wenjun; Dong, Zhenfang; Cheng, Shiqing; Liu, Yiqing; Qu, Teng; Wang, Xiaoying; Wang, Yong; Zhang, Bingchang; Ju, Ying

    2017-07-01

    T-cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) is preferentially expressed on terminally differentiated Th1 cells and inhibits their IFN-γ production. It has been reported that chronic inflammation may be an important driving force for myeloproliferative neoplasms (MPNs). Therefore, we hypothesized that as an important inflammation regulator, TIM-3 may be involved in essential thrombocythaemia (ET). The goal of this study was to investigate whether the -1516G > T, -574G > T and +4259T > G single-nucleotide polymorphisms (SNPs) within the TIM-3 gene contribute to the genetic susceptibility of individuals to ET. Genotyping of the TIM-3 -1516G > T, -574G > T and + 4259T > G SNPs was performed in 175 patients with ET and in 151 controls via a polymerase chain reaction-restriction fragment length polymorphism assay. We also investigated the relationships between the genotypes of each SNP and the risk factors of ET such as routine blood indexes, age and JAK2 V617F mutation. The genotype and allele frequencies of the -1516G > T SNP (p = 0.016 and 0.019, respectively), the -574G > T SNP (p = 0.035 and 0.038, respectively) and the +4259T > G SNP (p = 0.036 and 0.038, respectively) of the ET patients and the controls were significantly different. A haplotype analysis found that the GGT and TGT haplotypes had significantly different distributions between ET and controls (p = 0.041 and 0.041, respectively). However, no significant differences were detected between the genotypes of all SNPs and routine blood indexes, age and JAK2V617F mutation. The -1516G > T, -574G > T and +4259T > G SNPs within TIM-3 gene might play an important role as a genetic risk factor in the pathogenesis of ET.

  13. Acute Hemorrhagic Encephalitis Responding to Combined Decompressive Craniectomy, Intravenous Immunoglobulin, and Corticosteroid Therapies: Association with Novel RANBP2 Variant

    Directory of Open Access Journals (Sweden)

    Abdulla Alawadhi

    2018-03-01

    Full Text Available BackgroundAcute hemorrhagic encephalomyelitis (AHEM is considered as a rare form of acute disseminated encephalomyelitis characterized by fulminant encephalopathy with hemorrhagic necrosis and most often fatal outcome.ObjectiveTo report the association with Ran Binding Protein (RANBP2 gene variant and the response to decompressive craniectomy and high-dose intravenous methylprednisolone (IVMP in life-threatening AHEM.DesignSingle case study.Case reportA 6-year-old girl known to have sickle cell disease (SCD presented an acquired demyelinating syndrome (ADS with diplopia due to sudden unilateral fourth nerve palsy. She received five pulses of IVMP (30 mg/kg/day. Two weeks after steroid weaning, she developed right hemiplegia and coma. Brain magnetic resonance imaging showed a left frontal necrotico-hemorrhagic lesion and new multifocal areas of demyelination. She underwent decompressive craniotomy and evacuation of an ongoing left frontoparietal hemorrhage. Comprehensive investigations ruled out vascular and infectious process. The neurological deterioration stopped concomitantly with combined neurosurgical drainage of the hematoma, decompressive craniotomy, IVMP, and intravenous immunoglobulins (IVIG. She developed during the following months Crohn disease and sclerosing cholangitis. After 2-year follow-up, there was no new neurological manifestation. The patient still suffered right hemiplegia and aphasia, but was able to walk. Cognitive/behavioral abilities significantly recovered. A heterozygous novel rare missense variant (c.4993A>G, p.Lys1665Glu was identified in RANBP2, a gene associated with acute necrotizing encephalopathy. RANBP2 is a protein playing an important role in the energy homeostasis of neuronal cells.ConclusionIn any ADS occurring in the context of SCD and/or autoimmune condition, we recommend to slowly wean steroids and to closely monitor the patient after weaning to quickly treat any recurrence of neurological symptom

  14. Association of tumor necrosis factor alpha gene polymorphism G-308A with pseudoexfoliative glaucoma in the Pakistani population.

    NARCIS (Netherlands)

    Khan, M.I.; Micheal, S.; Rana, N.; Akhtar, F.; Hollander, A.I. den; Ahmed, A.; Qamar, R.

    2009-01-01

    PURPOSE: The purpose of the present study was to determine the role of the tumor necrosis factor alpha (TNF-alpha) gene polymorphism G-308A and total serum immunoglobulin E (TsIgE) levels in the onset of pseudoexfoliation glaucoma (PEXG) in Pakistani patients. METHODS: The TNF-alpha polymorphism

  15. Mutation pattern in the Bruton's tyrosine kinase gene in 26 unrelated patients with X-linked agammaglobulinemia

    DEFF Research Database (Denmark)

    Vorechovský, I; Luo, L; Hertz, Jens Michael

    1997-01-01

    Mutation pattern was characterized in the Bruton's tyrosine kinase gene (BTK) in 26 patients with X-linked agammaglobulinemia, the first described immunoglobulin deficiency, and was related to BTK expression. A total of 24 different mutations were identified. Most BTK mutations were found to result...

  16. Intravenous immunoglobulin in the management of a rare cause of hemolytic disease of the newborn: Anti-SARA antibodies.

    Science.gov (United States)

    Venkataraman, Rohini; Yusuf, Kamran

    2017-01-01

    Hemolytic disease of newborn (HDN) is a condition that develops in a fetus, when the IgG molecules produced by the mother pass through the placenta and attack the fetal red blood cells. HDN can occur due to Rh and ABO incompatibilities between the mother and the fetus as well as due to other allo-immune antibodies belonging to Kell (K and k), Duffy (Fya), Kidd (Jka and Jkb), and MNS (M, N, S, and s) systems. Role of intravenous immunoglobulin in management of HDN is not clear.SARA red blood cell antigen, first discovered in 1990 is a low frequency antigen. We report, a multiparous female whose pregnancy was complicated by HDN due to anti-SARA antibodies requiring both exchange transfusion and intravenous immunoglobulin. The response was sustained after intravenous immunoglobulin (IVIG) rather than after exchange transfusion.

  17. Swine plasma immunoglobulins for prevention and treatment of post-weaning diarrhoea: Optimizing stability towards gut conditions

    DEFF Research Database (Denmark)

    Hedegaard, Chris Juul; Ballegaard, Anne-Sofie; Røjel, Nanna

    Brief description of research area: A common problem in swine production is diarrhoea in newly weaned piglets, and huge quantities of antibiotics go to treat post-weaning diarrhoeas in piglets. The use of antibiotics can lead to the development of multi- and fully resistant bacteria, which...... consequently pose a great threat to human health. Therefore, sustainable alternatives for treating post-weaning diarrhoea without using antibiotics are in demand. Swine that are old (and big) enough for slaughter have during their upbringing been challenges by many different pathogens and thus have developed...... know: It is possible to multimerise immunoglobulins, which results in an advantage when binding to their respective antigens in comparison to the non-multimerised immunoglobulins, but too high degree of multimerisation abates immunoglobulin reactivity. Unfortunately, a preliminary study showed...

  18. Primary vs. secondary antibody deficiency: clinical features and infection outcomes of immunoglobulin replacement.

    Directory of Open Access Journals (Sweden)

    Sai S Duraisingham

    Full Text Available Secondary antibody deficiency can occur as a result of haematological malignancies or certain medications, but not much is known about the clinical and immunological features of this group of patients as a whole. Here we describe a cohort of 167 patients with primary or secondary antibody deficiencies on immunoglobulin (Ig-replacement treatment. The demographics, causes of immunodeficiency, diagnostic delay, clinical and laboratory features, and infection frequency were analysed retrospectively. Chemotherapy for B cell lymphoma and the use of Rituximab, corticosteroids or immunosuppressive medications were the most common causes of secondary antibody deficiency in this cohort. There was no difference in diagnostic delay or bronchiectasis between primary and secondary antibody deficiency patients, and both groups experienced disorders associated with immune dysregulation. Secondary antibody deficiency patients had similar baseline levels of serum IgG, but higher IgM and IgA, and a higher frequency of switched memory B cells than primary antibody deficiency patients. Serious and non-serious infections before and after Ig-replacement were also compared in both groups. Although secondary antibody deficiency patients had more serious infections before initiation of Ig-replacement, treatment resulted in a significant reduction of serious and non-serious infections in both primary and secondary antibody deficiency patients. Patients with secondary antibody deficiency experience similar delays in diagnosis as primary antibody deficiency patients and can also benefit from immunoglobulin-replacement treatment.

  19. Primary vs. Secondary Antibody Deficiency: Clinical Features and Infection Outcomes of Immunoglobulin Replacement

    Science.gov (United States)

    Duraisingham, Sai S.; Buckland, Matthew; Dempster, John; Lorenzo, Lorena; Grigoriadou, Sofia; Longhurst, Hilary J.

    2014-01-01

    Secondary antibody deficiency can occur as a result of haematological malignancies or certain medications, but not much is known about the clinical and immunological features of this group of patients as a whole. Here we describe a cohort of 167 patients with primary or secondary antibody deficiencies on immunoglobulin (Ig)-replacement treatment. The demographics, causes of immunodeficiency, diagnostic delay, clinical and laboratory features, and infection frequency were analysed retrospectively. Chemotherapy for B cell lymphoma and the use of Rituximab, corticosteroids or immunosuppressive medications were the most common causes of secondary antibody deficiency in this cohort. There was no difference in diagnostic delay or bronchiectasis between primary and secondary antibody deficiency patients, and both groups experienced disorders associated with immune dysregulation. Secondary antibody deficiency patients had similar baseline levels of serum IgG, but higher IgM and IgA, and a higher frequency of switched memory B cells than primary antibody deficiency patients. Serious and non-serious infections before and after Ig-replacement were also compared in both groups. Although secondary antibody deficiency patients had more serious infections before initiation of Ig-replacement, treatment resulted in a significant reduction of serious and non-serious infections in both primary and secondary antibody deficiency patients. Patients with secondary antibody deficiency experience similar delays in diagnosis as primary antibody deficiency patients and can also benefit from immunoglobulin-replacement treatment. PMID:24971644

  20. Identification and Extraction of Chicken Egg Yolk Immunoglobulin from Egg by Polyethylene Glycol (PEG Precipitation

    Directory of Open Access Journals (Sweden)

    Mohammad Mehdi Soltan Dallal

    2016-01-01

    Full Text Available Background: Staphylococcus aureus strains exhibiting multiple antibiotic resistances are isolatedfrom most communities and hospital infections. Treatment of patients with these infections hasbeen difficult. The aim of this study was to detect and extract, the egg yolk immunoglobulin Y asa potential source of anti- S. aureus antibody.Methods: Specific IgY was produced by immunizing hens with formalin-killed S. aureus. Thespecificity of serum`s antibody was confirmed by ELISA method. The antibodies were extractedfrom egg yolk by polyethylene glycol (PEG precipitation. Proteins were analysed by sodiumdodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE.Results: Chicken egg yolk antibodies (IgY were raised against S. aureus in the serum afterinjections. Up to 104 dilution specific antibodies were determined in serum.Conclusion: The results of the ELISA indicates the specificity of the immunoglobulin Y to thetarget antigen. In order to find a viable alternative to antibiotic treatments, more research must bedone on the ability of these antibodies to inhibit the growth of S. aureus.

  1. [Use of monoclonal antibodies against horse immunoglobulin in an enzyme immunoassay of bacterial toxins and anatoxins].

    Science.gov (United States)

    Burkin, M A; Gal'vidis, I A; Iakovleva, I V; Sviridov, V V

    2007-01-01

    Immunization of BALB/c mice by horse antiserum against diphtheria made it possible to obtain IgG1 monoclonal antibodies (MoAbs) 2B7E4 specific for light chains of horse immunoglobulin (Ig). Unlike commercial preparations of anti-horse immunoglobulin antibodies, which are specific for the whole Ig molecule or its Fc-fragment, the peroxidase (HRP) conjugate of the MoAb, 2B7E4-HRP did not interact with human, mouse, rabbit, and sheep Igs, or horse albumin. The conjugate obtained was used with MoAbs against bacterial toxins and commercial horse anatoxins, as a universal reagent in sandwich enzyme immunoassay (ELISA) for bacterial toxins and anatoxins. The detection sensitivity of diphtheria toxin/anatoxin equaled 0.0005 Lf/ml; tetanus toxin and anatoxin were detected with sensitivities of 20 LD50/ml and 0.005 UI/ml, respectively. A similar sandwich ELISA for botulinum anatoxins (group measurement) allowed types A, B, and E to be detected at 0.02, 0.002, and 0.001 UI/ml, respectively; selective measurement was only possible in the case of type E anatoxin (0.001 UI/ml).

  2. Experience with polyclonal immunoglobulin therapy in poly trauma patients with severe sepsis

    International Nuclear Information System (INIS)

    Janjua, S.K.; Hussain, R.M.; Mohsin, S.T.; Iqbal, A.; Mishwani, A.H.

    2011-01-01

    To evaluate the effects of intravenous immunoglobulin therapy on progression of severe sepsis in patients of poly trauma. Design: Quasi-experimental study. Place and Duration of Study: Combined Military Hospital Peshawar from June 2008 to Dec 2009. Patients and Methods: Forty six patients of poly trauma with severe sepsis were included. Along with the standard management i.e., surgical management, fluid resuscitation, antibiotics, analgesics, ionotropic, ventilatory and nutritional support, IVIG 5% (intravenous immunoglobulin) was infused over a period of 6 hours and repeated for three consecutive days. Sequential Organ Failure Assessment (SOFA) score was used to assess the progress in all the patients. Results: At the time of enrolment mean SOFA score was 5.41+- 1.127 and on the 15 day it was 1.62 +- 2.24, mean age was 39.21+10.26 years. Thirty four patients (73.91%) developed gram negative sepsis and eighteen patients (39.13%) developed septic shock. Mean duration of stay in ICU and on ventilatory support was 20.80+9.61 and 10.52 + 5.52 days respectively. Thirty five days mortality rate of these patients was 30.43%. Conclusion: The IVIG administration, when used along with the standard management appears to improve significantly the prognosis in patients of poly trauma with severe sepsis. (author)

  3. Characterization of the immunoglobulin repertoire of the spiny dogfish (Squalus acanthias).

    Science.gov (United States)

    Smith, Lauren E; Crouch, Kathryn; Cao, Wei; Müller, Mischa R; Wu, Leeying; Steven, John; Lee, Michael; Liang, Musen; Flajnik, Martin F; Shih, Heather H; Barelle, Caroline J; Paulsen, Janet; Gill, Davinder S; Dooley, Helen

    2012-04-01

    The cartilaginous fish (chimeras, sharks, skates and rays) are the oldest group relative to mammals in which an adaptive immune system founded upon immunoglobulins has been found. In this manuscript we characterize the immunoglobulins of the spiny dogfish (Squalus acanthias) at both the molecular and expressed protein levels. Despite the presence of hundreds of IgM clusters in this species the serum levels of this isotype are comparatively low. However, analysis of cDNA sequences and serum protein suggests microheterogeneity in the IgM heavy chains and supports the proposal that different clusters are preferentially used in the two forms (monomer or pentamer) of this isotype. We also found that the IgNAR isotype in this species exists in a previously unknown multimeric format in serum. Finally, we identified a new form of the IgW isotype (the shark IgD orthologue), in which the leader is spliced directly to the first constant domain, resulting in a molecule lacking an antigen-binding domain. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Effect of Ramadan fasting in Saudi Arabia on serum bone profile and immunoglobulins.

    Science.gov (United States)

    Bahijri, Suhard M; Ajabnoor, Ghada M; Borai, Anwar; Al-Aama, Jumana Y; Chrousos, George P

    2015-10-01

    Each year Muslims fast from dawn to sunset for 1 month (Ramadan). In Saudi Arabia, the sleep-wake cycle during Ramadan is severely disturbed and is associated with abolition of the circadian cortisol rhythm, exposing Saudis to continuously increased cortisol levels, which may influence the immune response. In addition to cortisol, sleep and fasting affect the secretion of parathyroid hormone (PTH) and hence bone metabolism. Our objective was to investigate the effect of Ramadan type fasting on secretory patterns of PTH, markers of bone metabolism, and serum immunoglobulins. Blood samples from healthy young volunteers were collected at 9 a.m. and 9 p.m. (± 1 hour) before (Shaban) and 2 weeks into Ramadan. Calcium, phosphorus, magnesium, albumin, alkaline phosphatase, 25-OH vitamin D, intact PTH (iPTH), and immunoglobulin (Ig) A, M and G were measured. During Ramadan, evening-adjusted calcium was higher (p = 0.036) and phosphate lower (p Ramadan mean morning phosphate was higher and the evening level lower was than Shabaan values (p = 0.010 and p Ramadan (p = 0.003 and p = 0.021 for morning and evening, respectively). Changes in dietary practices during Ramadan modulated PTH secretion to a pattern which might be beneficial to bone health. Combined effects of fasting and disturbed sleep led to a noted decrease in IgG level. Therefore, a possible beneficial effect of fasting on bone turnover is combined with decreased immune response.

  5. Lymphoid irradiation in intractable rheumatoid arthritis: effects on the production of immunoglobulins and rheumatoid factors

    International Nuclear Information System (INIS)

    Hanly, J.G.; Bresnihan, B.; Hassan, J.; Whelan, A.; Feighery, C.; Moriarty, M.

    1985-01-01

    Changes in the production of immunoglobulins and rheumatoid factors (RF's) were studied in 20 patients with intractable rheumatoid arthritis (RA) following total doses of 750 rad or 2,000 rad lymphoid irradiation. Over a 12 month follow up period there was no consistent change in absolute serum or synovial fluid levels, or in synovial membrane production of either total IgG, IgA or IgM, or the corresponding RF fractions. The in-vitro production of immunoglobulins and IgM RF by peripheral blood mononuclear cells was also unaltered, except for one patient who had a dramatic rise in IgM RF production. Over the same period there was a significant overall reduction in disease activity following both doses of radiotherapy. It is concluded that the clinical response which occurs following lymphoid irradiation is not due to a reduction in RF production. Furthermore, the production of RF's appears to be unaffected by the changes in T cell immunity which occur following lymphoid irradiation. (author)

  6. Comparison of Major Immunoglobulins Intrathecal Synthesis Patterns in Ecuadorian and Cuban Patients with Angiostrongyliasis

    Science.gov (United States)

    Padilla-Docal, Bárbara; Dorta-Contreras, Alberto J.; Moreira, Juan M.; Martini-Robles, Luiggi; Muzzio-Aroca, Jenny; Alarcón, Fernando; Magraner-Tarrau, María Esther; Bu-Coifiu-Fanego, Raisa

    2011-01-01

    Angiostrongylus cantonensis meningitis was first reported in Cuba in 1981, and it was recently reported in South America. The aim of this paper is to evaluate the intrathecal immunoglobulin synthesis patterns from Cuba's and Ecuador's patients with angiostrongyliasis; 8 Ecuadorian patients from two different outbreaks and 28 Cuban patients were studied. Simultaneous blood and cerebrospinal fluid simples were taken. Immunoglobulin (Ig) A, IgM, IgG, and albumin were quantified by radial immunodiffusion. Corresponding Reibergrams were applied. A three-Ig pattern was the most frequent in the two groups, but IgM was presented in all Ecuadorian young mature patients; however, in the Cuban children, only 12 of 28 patients had intrathecal IgM, but about 90% had an IgA and IgG synthesis at time of later puncture. This indicates that, with a larger amount of parasites ingested, clinical symptoms are more severe, and a higher frequency of intrathecal IgM synthesis could be observed. This is discussed as a similarity with the intrathecal IgM synthesis in African trypanosomiasis. PMID:21363978

  7. Technology of DTPA and immunoglobulins conjugation and their attachment to 90Y and 177Lu radionuclides

    International Nuclear Information System (INIS)

    Rekova, M.; Jedinakova-Krizova, V.

    2010-01-01

    The aim of the study of labeling of ligand-antibody conjugates was to find optimal conditions of preparing of these conjugates and appropriate radioactivity of selected nuclide for applications in nuclear medicine. Conjugation of the γ-immunoglobulin G (human or bovine IgG, polyclonal antibodies) and bifunctional chelating agent, diethylenetriaminepentaacetic acid dianhydride (cDTPAA), was carried out. Various values of the cDTPAA/antibody ratio, the weight concentration of polyclonal or monoclonal antibodies (MEM-97) and buffers were used. Further, the labeling conditions of the DTPA-IgG conjugate by radionuclides 90 Y and 177 Lu were optimized, and the labeling yield and the conjugation ratio of prepared radionuclide-DTPA-IgG conjugates was determined. Optimal incubation time of the immunoglobulin conjugation was obtained at 30 min from mixing of individual components. The labeling yield of radionuclide-DTPA-antibody conjugate higher than 95% was achieved. Higher values of conjugation ratio of radionuclide-DTPA-antibody conjugate were achieved in 0.1 mol L -1 carbonate buffer, pH 8.5, and the 0.1 mol L -1 carbonate buffer is suitable for studied conjugation systems. This study showed that the labeling yield as well as the conjugation ratio of tested systems depend on the amount of antibody substance, bifunctional chelating agent/antibody molar ratio and pH value of the buffer used. (author)

  8. On the dark side of therapies with immunoglobulin concentrates. The adverse events

    Directory of Open Access Journals (Sweden)

    Peter J. Spaeth

    2015-02-01

    Full Text Available Abstract to the dark side of therapies with human immunoglobulin G concentratesTherapy by human immunoglobulin G (IgG concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE profile of IgG concentrates which, even at life-long need for therapy, is excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current Good Manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below we review elements of non-infectious AEs , and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates.

  9. Massive immunoglobulin treatment in women with four or more recurrent spontaneous primary abortions of unexplained aetiology.

    Science.gov (United States)

    Yamada, H; Kishida, T; Kobayashi, N; Kato, E H; Hoshi, N; Fujimoto, S

    1998-09-01

    The aim of this trial was to investigate the efficacy of massive i.v. immunoglobulin (MIVIg) treatment for women with a history of recurrent spontaneous abortion (RSA) due to unexplained aetiology. The study included nine women (11 pregnancies) with a history of four or more consecutive RSA with unexplained aetiology and no live births. The mean number of fetal losses was 4.5 (range 4-6 abortions). Over the course of 5 days, immunoglobulin (20 g/day) was infused i.v. at gestational weeks 4-7. No additional infusions were carried out. Two pregnancies out of the 11 conceptions resulted in missed abortions at gestational weeks 6 and 7 respectively. Mosaicism (46XX/ 48XX, +16, +20), and tetraploidy (92XXXX) were found by chromosome analyses of the two aborti. Eight out of the other nine pregnancies resulted in full term deliveries of healthy neonates. One pregnancy developed intrauterine growth retardation and fetal distress, resulting in a premature delivery (30 gestational weeks) by Caesarean section. Thus, excluding the two abortions with chromosome aberrations, the MIVIg treatment was effective in all nine pregnancies of RSA women with unexplained aetiology. This MIVIg treatment (100 g administered in early gestation) may be a beneficial alternative to previous IVIg infusion methods, and should be further evaluated in a multicentric, placebo-controlled study, employing a larger number of homogeneous patients who fall into a high risk category of first trimester abortions.

  10. T-cell independent reconstitution of the immunoglobulin levels in nu/nu mice

    International Nuclear Information System (INIS)

    Mannhardt, W.; Schulte-Wissermann, H.; Gardilcic, S.; Leon, F. de

    1982-01-01

    Nude mice were transplanted under the renal capsule either with allogeneic or human thymus that were long-term precultured or pretreated in vitro with Carrageenan for three days. None of the thymus tissue transplants showed lymphatic repopulation 9 wk after transplantation. Histological investigation of the peripheral lymphatic tissue did not reveal any change in the thymus-dependent area. On the other hand, plasma cells and germinal centers could be found in significantly increased numbers. In addition, a normalization of the serum immunoglobulin concentrations could be found, as no specific antibodies against thymus-dependent antigens were present after immunization and T-cell function did not improve. Similar results were obtained 9 wk after injection of irradiated thymocyte suspensions or of peritoneal macrophages from immunocompetent donors. It is concluded that thymus epithelial cells could act via macrophages on the polyclonal maturation and differentiation of B cells without involvement of T cells. This would be in agreement with the experience in some patients with severe combined immunodeficiency (SCID) in which reconstitution of the immunoglobulin levels is observed after transplantation of cultured thymus tissue before T-cell reconstitution can be demonstrated. (Auth.)

  11. Differential immunoadsorption coupled with rate nephelometry for estimation of DNA-binding immunoglobulins

    International Nuclear Information System (INIS)

    DeBari, V.A.; Nicotra, J.; Blaney, J.F.; Schultz, E.F.; Needle, M.A.

    1984-01-01

    The authors describe a technique for estimating the mass of anti-DNA antibodies by immunonephelometry of serum immunoglobulins (IgG, IgA, IgM) before and after adsorption onto DNA bound to agarose-polylysine columns. Sixteen patients with systemic lupus erythematosus and 16 age- and sex-matched controls were studied. Precision was determined for high-value (in 10 patients) and low-value (in nine controls) ranges for each of the immunoglobulins. They found anti-DNA antibody concentrations (mean +/- SD) in systemic lupus erythematosus of 1.981 +/- 1.015 g/L for IgG 0.257 +/- 0.215 g/L for IgA and 0.282 +/- 0.234 g/L for IgM. Sensitivity and linearity are such that fivefold dilutions of patients' serum with either a buffered albumin solution or control serum yielded values close to the expected values for IgG. Similarly diluted sera gave inordinately high values in the radiometric binding assay. Neither parametric (linear regression) nor nonparametric correlation methods (Spearman's rank and Kendall's tau) show a significant correlation between patients' data obtained by the present technique and that by a radiometric binding assay, although combined data from patients and controls demonstrate a significant nonparametric correlation

  12. Simple immunoglobulin G sensor based on thin core single-mode fiber

    Science.gov (United States)

    Zheng, Yingfang; Lang, Tingting; Shen, Tingting; Shen, Changyu

    2018-03-01

    In this paper, a simple fiber biosensor (FOB) for immunoglobulin G (IgG) detection is designed and experimentally verified. The FOB is constructed by a 20 mm long thin core single-mode fiber (TCSMF) sandwiched between two single-mode optical fibers (SMFs). First, the refractive index (RI) sensitivity of the fiber structures is calculated by the beam propagation method. The refractive index sensing experiment is performed using different concentrations of glycerol solutions, and the experimental results are mostly consistent with the simulation predictions. The experimental RI sensitivity increases with the surrounding RI and reaches 82.7 nm/RIU. Then the surface of the FOB is functionalized by APTES for covalent bonding. The human IgG and goat anti-human IgG are chosen as a bioconjugated pair to examine the bio-sensing effectiveness of this FOB. The sensitivity of IgG detection is determined to be 10.4 nm/(mg/ml). And the serum IgG concentration in normal adults lies within the range of 6-16 mg/ml (Worsfold et al., 1985), so the sensor is applicable to human IgG monitoring. The specificity of the FOB is also verified by a contrast experiment conducted using rabbit immunoglobulin G. The proposed FOB is simple, low loss, cost-effective, and can be used for various biological and chemical applications.

  13. Effect of Holder pasteurization on macronutrients and immunoglobulin profile of pooled donor human milk.

    Science.gov (United States)

    Adhisivam, B; Vishnu Bhat, B; Rao, Krishna; Kingsley, S M; Plakkal, Nishad; Palanivel, C

    2018-03-27

    The objective of this study was to study the effect of Holder pasteurization on macronutrients and immunoglobulin profile of pooled donor human milk. This descriptive study was conducted in a Human Milk Bank of a tertiary care teaching institute in south India. Thirty random paired pooled donor human milk samples (before and after pasteurization) were analyzed for macronutrients (protein, fat, carbohydrates) using infrared spectroscopy. Similarly, immunoglobulin profile (IgA and IgG) before and after pasteurization was quantified using ELISA. The mean values of protein, fat, and carbohydrates in pooled donor milk pre-pasteurization were 1.6, 3.6, and 6.1 g/dl compared with post-pasteurization values 1.4, 2.7, and 5.9 g/dl, respectively. Pasteurization reduced protein, fat, and energy content of pooled donor milk by 12.5%, 25%, and 16%, respectively. However, carbohydrates were not significantly reduced. Pasteurization decreased IgA by 30% and IgG by 60%. Holder pasteurization of pooled donor human milk decreases protein, fat, and energy content and also reduces the levels of IgA and IgG.

  14. Characterizing immunoglobulin repertoire from whole blood by a personal genome sequencer.

    Directory of Open Access Journals (Sweden)

    Fan Gao

    Full Text Available In human immune system, V(DJ recombination produces an enormously large repertoire of immunoglobulins (Ig so that they can tackle different antigens from bacteria, viruses and tumor cells. Several studies have demonstrated the utility of next-generation sequencers such as Roche 454 and Illumina Genome Analyzer to characterize the repertoire of immunoglobulins. However, these techniques typically require separation of B cell population from whole blood and require a few weeks for running the sequencers, so it may not be practical to implement them in clinical settings. Recently, the Ion Torrent personal genome sequencer has emerged as a tabletop personal genome sequencer that can be operated in a time-efficient and cost-effective manner. In this study, we explored the technical feasibility to use multiplex PCR for amplifying V(DJ recombination for IgH, directly from whole blood, then sequence the amplicons by the Ion Torrent sequencer. The whole process including data generation and analysis can be completed in one day. We tested the method in a pilot study on patients with benign, atypical and malignant meningiomas. Despite the noisy data, we were able to compare the samples by their usage frequencies of the V segment, as well as their somatic hypermutation rates. In summary, our study suggested that it is technically feasible to perform clinical monitoring of V(DJ recombination within a day by personal genome sequencers.

  15. Correlation between parity and concentration of immunoglobulins A, G and M in human colostrum

    Directory of Open Access Journals (Sweden)

    Gabriel André João Striker

    2003-06-01

    Full Text Available Objective: To study the relationship between parity andimmunoglobulin concentrations in human colostrum. Methods:82 puerperas aged 21-41 years were selected, with gestationalage ≥ 37 weeks, up to the fourth parity, good nutritional status andno gestational or puerperal diseases. The inclusion criteria for thenewborn were: weight > 2,500 g, Apgar score > 7 in the firstminute and exclusive maternal breastfeeding until discharge fromthe nursery. The mothers were divided into 2 groups: A -primiparous, B - multiparous. Colostrum was collected manuallyfrom 48 to 72 hours after delivery and the immunoglobulins weremeasured by ELISA technique. Results: No differences wereobserved regarding timing to collect colostrum; the earliercolostrum was collected, the higher the concentration of immunoglobulinA; primiparous women showed higher concentrations of IgA andIgM in their colostrum than multiparous women; there were nodifferences regarding IgG concentrations in the two groups.Conclusion: Primiparous women presented higher concentrationsof IgA and IgM in their colostrum than multiparous women.

  16. Immunoglobulin levels in dogs after total-body irradiation and bone marrow transplantation

    International Nuclear Information System (INIS)

    Vriesendorp, H.M.; Halliwell, R.E.; Johnson, P.M.; Fey, T.A.; McDonough, C.M.

    1985-01-01

    The influence of total-body irradiation (TBI) and autologous or allogeneic bone marrow transplantation on serum immunoglobulin subclasses was determined in a dog model. Only IgG1 levels decreased after low-dose (+/- 4.5 Gy) TBI, but levels of all immunoglobulin classes fell after high-dose TBI (8.5 GyX1 or 2X6.0 Gy). After autologous bone marrow transplantation IgM levels were the first and IgE levels were the last to return to normal. After successful allogeneic bone marrow transplantation prolonged low IgM and IgE levels were found but IgA levels increased rapidly to over 150% of pretreatment values. A comparison of dogs with or without clinical signs or graft-versus-host disease (GVHD), revealed no differences in IgM levels. Dogs with GVHD had higher IgA but lower IgE levels. Dogs that rejected their allogeneic bone marrow cells showed significant early rises in IgE and IgA levels in comparison with dogs with GVHD. These results differ from the observations made on Ig levels in human bone marrow transplant patients. No significant differences in phytohemagglutinin stimulation tests were found between dogs with or without GVHD or dogs receiving an autologous transplant for the first four months after TBI and transplantation. An early primary or secondary involvement of humoral immunity in GVHD and graft rejection in dogs is postulated

  17. Diagnosis and activity assessment of immunoglobulin A nephropathy: current perspectives on noninvasive testing with aberrantly glycosylated immunoglobulin A-related biomarkers

    Directory of Open Access Journals (Sweden)

    Suzuki Y

    2014-10-01

    Full Text Available Yusuke Suzuki,1 Hitoshi Suzuki,1 Yuko Makita,1 Akiko Takahata,1 Keiko Takahashi,1 Masahiro Muto,1 Yohei Sasaki,1 Atikemu Kelimu,1 Keiichi Matsuzaki,2 Hiroyuki Yanagawa,1 Keiko Okazaki,1 Yasuhiko Tomino1 1Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, 2Kyoto University Health Service, Kyoto, Japan Abstract: Immunoglobulin (Ig A nephropathy (IgAN is the most common form of glomerular disease worldwide and is associated with a poor prognosis. Thus, development of a curative treatment and strategies for early diagnosis and treatment are urgently needed. Pathological analysis of renal biopsy is the gold standard for the diagnosis and assessment of disease activity; however, immediate and frequent assessment based on biopsy specimens is difficult. Therefore, a simple and safe alternative is desirable. On the other hand, it is now widely accepted that multi-hit steps, including production of aberrantly glycosylated serum IgA1 (first hit, and IgG or IgA autoantibodies that recognize glycan containing epitopes on glycosylated serum IgA1 (second hit and their subsequent immune complex formation (third hit and glomerular deposition (fourth hit, are required for continued progression of IgAN. Although the prognostic and predictive values of several markers have been discussed elsewhere, we recently developed a highly sensitive and specific diagnostic method by measuring serum levels of glycosylated serum IgA1 and related IgA immune complex. In addition, we confirmed a significant correlation between serum levels of these essential effector molecules and disease activity after treatment, suggesting that each can be considered as a practical surrogate marker of therapeutic effects in this slowly progressive disease. Such a noninvasive diagnostic and activity assessment method using these disease-oriented specific biomarkers may be useful in the early diagnosis of and intervention in IgAN, with

  18. Gene Therapy

    Science.gov (United States)

    Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...

  19. Intravenous immunoglobulin treatment and screening for hypocretin neuron-specific autoantibodies in recent onset childhood narcolepsy with cataplexy

    DEFF Research Database (Denmark)

    Knudsen, S; Mikkelsen, J D; Bang, B

    2010-01-01

    Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC.......Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC....

  20. Investigations of immunoglobulins, circulating immune complexes and plasma free hemoglobin in cancer patients on 60Co gamma-ray therapy

    International Nuclear Information System (INIS)

    Horvath, M.; Rode, I.L.; Fekete, B.; Kiss, B.; Ringwald, G.

    1981-01-01

    32 patients with different tumours were irradiated by 60 Co gamma-rays. During therapy lasting for several weeks, changes in the content of immunoglobulin and of some other serum proteins, circulating immune complexes and plasma free hemoglobin were determined. Immunosuppression according to immunoglobulin content in serum was not produced by this type of radiation. Decrease in immune complex levels was a good prognostic sign. Low values of plasma hemoglobin content during treatment indicated that no erythrocyte membrane damage had been effected. (orig.) [de

  1. General practitioner views on the determinants of test ordering: a theory-based qualitative approach to the development of an intervention to improve immunoglobulin requests in primary care.

    LENUS (Irish Health Repository)

    Cadogan, S L

    2016-07-19

    Research suggests that variation in laboratory requesting patterns may indicate unnecessary test use. Requesting patterns for serum immunoglobulins vary significantly between general practitioners (GPs). This study aims to explore GP\\'s views on testing to identify the determinants of behaviour and recommend feasible intervention strategies for improving immunoglobulin test use in primary care.

  2. Sequence similarities of protein kinase substrates and inhibitors with immunoglobulins and model immunoglobulin homologue: cell adhesion molecule from the living fossil sponge Geodia cydonium. Mapping of coherent database similarities and implications for evolution of CDR1 and hypermutation

    Czech Academy of Sciences Publication Activity Database

    Kubrycht, J.; Borecký, Jiří; Souček, P.; Ježek, Petr

    2004-01-01

    Roč. 49, č. 3 (2004), s. 219-246 ISSN 0015-5632 R&D Projects: GA MZd NJ6747 Institutional research plan: CEZ:AV0Z5011922 Keywords : CDR1 * immunoglobulin Subject RIV: EE - Microbiology, Virology Impact factor: 1.034, year: 2004

  3. Frequency patterns of T-cell exposed motifs in immunoglobulin heavy chain peptides presented by MHCs

    Directory of Open Access Journals (Sweden)

    Robert D. Bremel

    2014-10-01

    Full Text Available Immunoglobulins are highly diverse protein sequences that are processed and presented to T-cells by B-cells and other antigen presenting cells. We examined a large dataset of immunoglobulin heavy chain variable regions (IGHV to assess the diversity of T-cell exposed motifs (TCEM. TCEM comprise those amino acids in a MHC-bound peptide which face outwards, surrounded by the MHC histotope, and which engage the T-cell receptor. Within IGHV there is a distinct pattern of predicted MHC class II binding and a very high frequency of re-use of the TCEMs. The re-use frequency indicates that only a limited number of different cognate T-cells are required to engage many different clonal B-cells. The amino acids in each outward-facing TCEM are intercalated with the amino acids of inward-facing MHC groove-exposed motifs (GEM. Different GEM may have differing, allele-specific, MHC binding affinities. The intercalation of TCEM and GEM in a peptide allows for a vast combinatorial repertoire of epitopes, each eliciting a different response. Outcome of T-cell receptor binding is determined by overall signal strength, which is a function of the number of responding T-cells and the duration of engagement. Hence, the frequency of T-cell exposed motif re-use appears to be an important determinant of whether a T-cell response is stimulatory or suppressive. The frequency distribution of TCEMs implies that somatic hypermutation is followed by clonal expansion that develop along repeated pathways. The observations of TCEM and GEM derived from immunoglobulins suggest a relatively simple, yet powerful, mechanism to correlate T-cell polyspecificity, through re-use of TCEMs, with a very high degree of specificity achieved by combination with a diversity of GEMs. The frequency profile of TCEMs also points to an economical mechanism for maintaining T-cell memory, recall, and self-discrimination based on an endogenously generated profile of motifs.

  4. Response pattern's of immunoglobulins evaluation in different lineages of mice infected with T. cruzi

    International Nuclear Information System (INIS)

    Silva, Andreia dos Santos

    2006-01-01

    The present work has employed different mice lineages (A/J, C57BL/6, B6AF1, BXA1 and BXA2) that were challenged with different doses of T. cruzi. The objective was to evaluate the pattern of immunoglobulins response presented by resistant and susceptible mice to T. cruzi as well as the lineages developed from the matting between them. So that evaluation was done by using lineages serums' sample, analyzed by ELISA's method. In agreement with the results observed all the lineages presented higher response to IgG2a and IgG2b, if compared with the titles to IgG1. IgG1 immunoglobulins involve a type Th2 pattern response which expressed allergic immunological responses, while IgG2 involves a pattern response Th1 that expresses cellular immunological response. The different lineages used in this research also presented different immunological response pattern by the infection with T. cruzi. Mice of the lineage C57BL/6 are resistant to the infection, while the animals of the lineage A/J are susceptible. The animals of the lineage B6AF1 are more resistant to the infection than their original parental C57BL/6. The immunological response developed by hybrid mice present traces of both susceptible and resistant parental A/J and C57BL/6, respectively. The animals of the lineage BXA1 can be considered resistant to the infection, but they don't present the same control as that presented by those of the lineages B6AF1 and C57BL/6. The animals of the lineage BXA2 can be considered susceptible to the infection, but they can control it for a long period, surviving like this, longer than the animals of the lineage A/J. In addition it was observed that the IgG2b immunoglobulins are very important to the resistance of mice to T. cruzi infection. (author)

  5. II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies.

    Science.gov (United States)

    Goudouris, Ekaterini Simões; Rego Silva, Almerinda Maria do; Ouricuri, Aluce Loureiro; Grumach, Anete Sevciovic; Condino-Neto, Antonio; Costa-Carvalho, Beatriz Tavares; Prando, Carolina Cardoso; Kokron, Cristina Maria; Vasconcelos, Dewton de Moraes; Tavares, Fabíola Scancetti; Silva Segundo, Gesmar Rodrigues; Barreto, Irma Cecília; Dorna, Mayra de Barros; Barros, Myrthes Anna; Forte, Wilma Carvalho Neves

    2017-01-01

    In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new knowledge about the indications and efficacy of immunoglobulin therapy in primary immunodeficiencies, relevant production-related aspects, mode of use (routes of administration, pharmacokinetics, doses and intervals), adverse events (major, prevention, treatment and reporting), patient monitoring, presentations available and how to have access to this therapeutic resource in Brazil. RESUMO Nos últimos anos, novas imunodeficiências primárias e defeitos genéticos têm sido descritos. Recentemente, produtos de imunoglobulina, com aprimoramento em sua composição e para uso por via subcutânea, tornaram-se disponíveis em nosso meio. Com o objetivo de orientar o médico no uso da imunoglobulina humana para o tratamento das imunodeficiências primárias, os membros do Grupo de Assessoria em Imunodeficiências da Associação Brasileira de Alergia e Imunologia produziram um documento que teve por base uma revisão narrativa da literatura e sua experiência profissional, atualizando o I Consenso Brasileiro publicado em 2010. Apresentam-se novos conhecimentos sobre indicações e eficácia do tratamento com imunoglobulina nas imunodeficiências primárias, aspectos relevantes sobre a produção, forma de utilização (vias de administração, farmacocinética, doses e intervalos), efeitos adversos (principais efeitos, prevenção, tratamento e notificação), monitorização do

  6. Inmunoglobulinas en pacientes con actinomicetoma por Nocardia brasiliensis Immunoglobulins in patients with Nocardia brasiliensis actinomycetoma

    Directory of Open Access Journals (Sweden)

    L. J. Méndez-Tovar

    2004-12-01

    Full Text Available Considerando que algunos autores han reportado un aumento en la cantidad de algunas inmunoglobulinas en los pacientes con actinomicetoma, en este trabajo nos propusimos determinar diferencias en la producción de IgG1, IgG2, IgG3, IgG4 e IgM en 25 pacientes con actinomicetoma por Nocardia brasiliensis y 25 personas sanas provenientes de una zona endémica de micetoma. La determinación de inmunoglobulinas se realizó por medio de la técnica de ELISA. Para sensibilizar las placas se emplearon 6 antígenos de N. brasiliensis: un antígeno crudo denominado NB y cinco derivados del mismo (NB2, NB4, NB6, NB8 y NB10 separados por punto isoeléctrico. Los niveles de las cuatro subclases de IgG fueron mayores en los sueros de los pacientes que en el suero de los controles, con una diferencia máxima en IgG3 e IgG4; para esta última subclase, los seis antígenos fueron altamente reactivos. La concentración de IgM fue igual en ambos grupos. Es probable que como ocurre en otras infecciones, en la fisiopatogenia del actinomicetoma influya no sólo el aumento o deficiencia de una clase de inmunoglobulina, sino la relación que existe entre las diferentes subclases.Considering that some authors have reported an increasing of some immunoglobulins in actinomycetoma patients, in this study we propose to determine differential production of IgG1, IgG2, IgG3, IgG4 and IgGM in 25 patients with actinomycetoma and 25 healthy individuals from a mycetoma endemic area. Immunoglobulins were determined by ELISA technique. To sensibilize the plates, six Nocardia brasiliensis antigens were used: a crude antigen denominated NB and five derivatives (NB2, NB4, NB6, NB8 and NB10 obtained by their isoelectric point. Results showed that all IgG subclasses were higher in the patients’ sera than in control sera, with a maximal difference to IgG3 and IgG4. To the latter subclass, six antigens were highly reactives. IgM levels were similar in both groups. As it occurs in other

  7. Giant hepatic artery aneurysm associated with immunoglobulin G4-related disease successfully treated using a liquid embolic agent

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, Michele; Virgilio, Edoardo; Laurino, Florindo; Orgera, Gianluigi; Mene, Paolo; Pirozzi, Nicola; Ziparo, Vincenzo; Cavallini, Marco [St. Andrea Hospital, Rome (Italy)

    2015-08-15

    The occurrence of a giant hepatic artery aneurysm (GHAA) in a patient with systemic vasculitis is very rare. Herein, we describe our endovascular treatment experience of a GHAA associated with immunoglobulin G4-related disease (IgG4-RD) consisting primarily of a liquid embolic injection and deployment of a vascular plug.

  8. The early postnatal development of salivary antibody and immunoglobulin response in chidren orally colonited with a nonpathogenic, probiotic strain

    Czech Academy of Sciences Publication Activity Database

    Vančíková, Z.; Lodinová-Žádníková, R.; Radl, J.; Tlaskalová, Helena

    2003-01-01

    Roč. 47, č. 2 (2003), s. 281-287 ISSN 0015-5632 R&D Projects: GA AV ČR IAA5020205 Institutional research plan: CEZ:AV0Z5020903 Keywords : immunoglobulins Subject RIV: EE - Microbiology, Virology Impact factor: 0.857, year: 2003

  9. Quantifying the reduction in immunoglobulin use over time in patients with chronic immune thrombocytopenic purpura receiving romiplostim (AMG 531)

    NARCIS (Netherlands)

    Pullarkat, Vinod A.; Gernsheirner, Terry B.; Wasser, Jeffrey S.; Newland, Adrian; Guthrie, Troy H.; de Wolf, Joost Th. M.; Stewart, Ron; Berger, Dietmar

    Patients with Immune thrombocytopenic purpura (ITP) often require immunoglobulin (Ig) therapy with intravenous 19 (IVIG) or anti-D to prevent or treat the serious bleeding events. Because the thrombopoietin (TPO) mimetic romiplostim (AMG 531; Nplate) elevates platelet counts in patients with chronic

  10. Prolonged in vivo residence times of llama single-domain antibody fragments in pigs by binding to porcine immunoglobulins

    NARCIS (Netherlands)

    Harmsen, M.M.; Solt, van C.B.; Fijten, H.P.D.; Setten, van M.C.

    2005-01-01

    The therapeutic parenteral application of llama single-domain antibody fragments (VHHs) is hampered by their small size, resulting in a fast elimination from the body. Here we describe a method to increase the serum half-life of VHHs in pigs by fusion to another VHH binding to porcine immunoglobulin

  11. Intravenous immunoglobulin treatment and screening for hypocretin neuron-specific autoantibodies in recent onset childhood narcolepsy with cataplexy

    DEFF Research Database (Denmark)

    Knudsen, S; Mikkelsen, J D; Bang, B

    2010-01-01

    Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC....

  12. Immunoglobulin preparations for intravenous administration. A review of their biologic activities and comparison of various preparation methods

    DEFF Research Database (Denmark)

    Nielsen, H

    1994-01-01

    procedures are employed by different commercial suppliers of immunoglobulins, and from the literature it appears that various important biologic functions, e.g., opsonic activity, complement fixation, and Fc-receptor function, are subject to alterations during the preparation. The best preservation...

  13. Evidence for Existence of Immunoglobulins that Block Ovarian Granulosa Cell Growth in Vitro. A Putative Role in Resistant Ovary Syndrome?

    NARCIS (Netherlands)

    WEISSENBRUCH, MIRJAM M. van; HOEK, ANNEMIEKE; VLIET-BLEEKER, INGRID van; SCHOEMAKER, JOOP; DREXHAGE, HEMMO

    1991-01-01

    The sera of 26 patients with premature ovarian failure were examined in order to detect immunoglobulin-G (IgGs) that can block FSH-induced in vitro granulosa cell DNA synthesis via, a Feulgen cytochemical bioassay system. The IgGs of four patients with polycystic ovary-like disease, five

  14. Separation of hemagglutination-inhibiting immunoglobulin M antibody to rubella virus in human serum by high-performance liquid chromatography.

    OpenAIRE

    Kobayashi, N; Suzuki, M; Nakagawa, T; Matumoto, M

    1986-01-01

    High-performance liquid chromatography was successfully used to separate hemagglutination-inhibiting immunoglobulin M (IgM) rubella virus antibody from IgG rubella virus antibody in human serum. The fractionation by high-performance liquid chromatography was as effective as sucrose density gradient centrifugation in separating IgM antibody from IgG antibody.

  15. The significance of platelet-associated immunoglobulin G in non-thrombocytopenic patients with systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Sørensen, P G; Mickley, H; Fristed, P

    1985-01-01

    The possible pathogenetic significance of platelet-associated immunoglobulin G in systemic lupus erythematosus (SLE) has been studied, using a semiquantitative immunofluorescence technique. The study included 22 patients suffering from SLE during the period 1973-81. Thirteen patients had various ...

  16. Immunochromatographic Brucella-specific immunoglobulin M and G lateral flow assays for rapid serodiagnosis of human brucellosis

    NARCIS (Netherlands)

    Smits, Henk L.; Abdoel, Theresia H.; Solera, Javier; Clavijo, Encarnacion; Diaz, Ramon

    2003-01-01

    To fulfill the need for a simple and rapid diagnostic test for human brucellosis, we used the immunochromatographic lateral flow assay format to develop two assays, one for the detection of Brucella-specific immunoglobulin M (IgM) antibodies and one for the detection of Brucella-specific IgG

  17. Immunoglobulin E and G4 antibody responses in occupational airway exposure to bovine and porcine plasma proteins

    NARCIS (Netherlands)

    Krop, E. J. M.; Stapel, S. O.; de Vrieze, H.; van der Zee, J. S.

    2006-01-01

    BACKGROUND: Production of both antigen-specific immunoglobulin (Ig)E and IgG4 antibodies is dependent on stimulation of B cells by T helper 2 cell-derived cytokines. However, there is controversy as to their interaction. In this study, we investigated the interdependency of IgE and IgG4 antibody

  18. Evaluation of diphtheria convalescent patients to serve as donors for the production of anti-diphtheria immunoglobulin preparations

    NARCIS (Netherlands)

    Bissumbhar, B.; Rakhmanova, A.G.; Berbers, G.; Iakolev, A.; Nosikova, E.; Melnick, O.; Ovtcharenko, E.; Rümke, H. C.; Ruitenberg, E.J.

    2004-01-01

    Aims: The study was conducted to evaluate the possibility of selecting convalescent diphtheria patients to serve in emergency situations as donors for the production of anti-diphtheria immunoglobulin. To select suitable donors, the criterion of an antitoxin titer ≥3.0 IU/ml was used. In addition,

  19. Giant hepatic artery aneurysm associated with immunoglobulin G4-related disease successfully treated using a liquid embolic agent

    International Nuclear Information System (INIS)

    Rossi, Michele; Virgilio, Edoardo; Laurino, Florindo; Orgera, Gianluigi; Mene, Paolo; Pirozzi, Nicola; Ziparo, Vincenzo; Cavallini, Marco

    2015-01-01

    The occurrence of a giant hepatic artery aneurysm (GHAA) in a patient with systemic vasculitis is very rare. Herein, we describe our endovascular treatment experience of a GHAA associated with immunoglobulin G4-related disease (IgG4-RD) consisting primarily of a liquid embolic injection and deployment of a vascular plug

  20. Is dosing of therapeutic immunoglobulins optimal? A review of a three-decade long debate in europe

    NARCIS (Netherlands)

    Kerr, Jacqueline; Quinti, Isabella; Eibl, Martha; Chapel, Helen; Späth, Peter J.; Sewell, W. A. Carrock; Salama, Abdulgabar; van Schaik, Ivo N.; Kuijpers, Taco W.; Peter, Hans-Hartmut

    2014-01-01

    The consumption of immunoglobulins (Ig) is increasing due to better recognition of antibody deficiencies, an aging population, and new indications. This review aims to examine the various dosing regimens and research developments in the established and in some of the relevant off-label indications

  1. Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers

    NARCIS (Netherlands)

    Lauc, G.; Huffman, J.E.; Pucic, M.; Zgaga, L.; Adamczyk, B.; Muzinic, A.; Novokmet, M.; Polasek, O.; Gornik, O.; Kristic, J.; Keser, T.; Vitart, V.; Scheijen, B.; Uh, H.W.; Molokhia, M.; Patrick, A.L.; McKeigue, P.; Kolcic, I.; Lukic, I.K.; Swann, O.; Leeuwen, F.N. van; Ruhaak, L.R.; Houwing-Duistermaat, J.J.; Slagboom, P.E.; Beekman, M.; Craen, A.J. de; Deelder, A.M.; Zeng, Q.; Wang, W.; Hastie, N.D.; Gyllensten, U.; Wilson, J.F.; Wuhrer, M.; Wright, A.F.; Rudd, P.M.; Hayward, C.; Aulchenko, Y.; Campbell, H.; Rudan, I.

    2013-01-01

    Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. After isolating IgG from human plasma, we performed 77 quantitative

  2. A fast and simple dot-immunobinding assay for quantifiction of mouse immunoglobulins in hybridoma culture supernatants

    Czech Academy of Sciences Publication Activity Database

    Sulimenko, Tetyana; Dráber, Pavel

    2004-01-01

    Roč. 289, - (2004), s. 89-95 ISSN 0022-1759 R&D Projects: GA AV ČR IBS5052301; GA MŠk LN00A026; GA MŠk 1P04OE158 Keywords : dot-immunobinding assay * hybridoma culture superntatants * mouse immunoglobulins Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.464, year: 2004

  3. Distribution of kappa and lambda light chain isotypes among human blood immunoglobulin-secreting cells after vaccination with pneumococcal polysaccharides

    DEFF Research Database (Denmark)

    Heilmann, C; Barington, T

    1989-01-01

    The light chain isotype of immunoglobulin-secreting blood cells was investigated by means of monolayer plaque-forming cell assays allowing direct immunofluorescence staining for cytoplasmic kappa and lambda light chains in centre cells. The study revealed that cultured, polyclonally activated...

  4. Effect of maternal dry period length on colostrum immunoglobulin content and natural and specific antibody titers in calves

    NARCIS (Netherlands)

    Mayasari, N.; Vries Reilingh, de G.; Nieuwland, M.G.B.; Remmelink, G.J.; Parmentier, H.K.; Kemp, B.; Knegsel, van A.T.M.

    2015-01-01

    The objective was to study the effect of dry period length in dairy cows on immunoglobulin content and natural antibodies (NAb) titers in colostrum, growth, and plasma natural and specific antibody titers in plasma of calves. Holstein-Friesian dairy cows (n = 167) were randomly assigned to 3 dry

  5. Elevated levels of total and dengue virus-specific immunoglobulin E in patients with varying disease severity

    NARCIS (Netherlands)

    Koraka, Penelopie; Murgue, Bernadette; Deparis, Xavier; Setiati, Tatty E.; Suharti, Catarina; van Gorp, Eric C. M.; Hack, C. E.; Osterhaus, Albert D. M. E.; Groen, Jan

    2003-01-01

    The kinetics of total and dengue virus-specific immunoglobulin E (IgE) were studied in serial serum samples obtained from 168 patients, 41 of whom suffered from primary dengue virus infection and 127 suffered from secondary dengue virus infection. Seventy-one patients were classified as dengue

  6. Elevated levels of total and dengue virus-specific immunoglobulin E in patients with varying disease severity.

    NARCIS (Netherlands)

    Koraka, P.; Murgue, B.; Deparis, X.; Setiati, T.E.; Suharti, C.; Gorp, E. van; Hack, C.E.; Osterhaus, A.D.; Groen, J.

    2003-01-01

    The kinetics of total and dengue virus-specific immunoglobulin E (IgE) were studied in serial serum samples obtained from 168 patients, 41 of whom suffered from primary dengue virus infection and 127 suffered from secondary dengue virus infection. Seventy-one patients were classified as dengue

  7. Target-specific activation of mast cells by immunoglobulin E reactive with a renal cell carcinoma-associated antigen

    NARCIS (Netherlands)

    Luiten, R. M.; Fleuren, G. J.; Warnaar, S. O.; Litvinov, S. V.

    1996-01-01

    Immunoglobulin E (IgE) that specifically binds to antigens present on carcinoma cells may represent a useful tool to combat carcinomas. Induction of an inflammatory response at the tumor site by tumor-specific IgE may result in reduced tumor growth and tumor regression. Local mast cells may be

  8. Herpes simplex virus immunoglobulin G Fc receptor activity depends on a complex of two viral glycoproteins, gE and gI

    International Nuclear Information System (INIS)

    Johnson, D.C.; Ligas, M.W.; Frame, M.C.; Cross, A.M.; Stow, N.D.

    1988-01-01

    Evidence was recently presented that herpes simplex virus type 1 (HSV-1) immunoglobulin G (IgG) Fc receptors are composed of a complex containing a previously described glycoprotein, gE, and a novel virus-induced polypeptide, provisionally named g70. Using a monoclonal antibody designated 3104, which recognizes g70, in conjunction with antipeptide sera and virus mutants unable to express g70 or gE, the authors have mapped the gene encoding g70 to the US7 open reading frame of HSV-1 adjacent to the gE gene. Therefore, g70 appears to be identical to a recently described polypeptide which was named gI. Under mildly denaturing conditions, monoclonal antibody 3104 precipitated both gI and gE from extracts of HSV-1-infected cells. In addition, rabbit IgG precipitated the gE-gI complex from extracts of cells transfected with a fragment of HSV-1 DNA containing the gI, gE, and US9 genes. Cells infected with mutant viruses which were unable to express gE or gI did not bind radiolabeled IgG; however, cells coinfected with two viruses, one unable to express gE and the other unable to express gI, bound levels of IgG approaching those observed with wild-type viruses. These results further support the hypothesis that gE and gI form a complex which binds IgG by the Fc domain and that neither polypeptide alone can bind IgG

  9. Anti-HIV double variable domain immunoglobulins binding both gp41 and gp120 for targeted delivery of immunoconjugates.

    Directory of Open Access Journals (Sweden)

    Ryan B Craig

    Full Text Available BACKGROUND: Anti-HIV immunoconjugates targeted to the HIV envelope protein may be used to eradicate the latent reservoir of HIV infection using activate-and-purge protocols. Previous studies have identified the two target epitopes most effective for the delivery of cytotoxic immunoconjugates the CD4-binding site of gp120, and the hairpin loop of gp41. Here we construct and test tetravalent double variable domain immunoglobulin molecules (DVD-Igs that bind to both epitopes. METHODS: Synthetic genes that encode DVD-Igs utilizing V-domains derived from human anti-gp120 and anti-gp41 Abs were designed and expressed in 293F cells. A series of constructs tested different inter-V-linker domains and orientations of the two V domains. Antibodies were tested for binding to recombinant Ag and native Env expressed on infected cells, for neutralization of infectious HIV, and for their ability to deliver cytotoxic immunoconjugates to infected cells. FINDINGS: The outer V-domain was the major determinant of binding and functional activity of the DVD-Ig. Function of the inner V-domain and bifunctional binding required at least 15 AA in the inter-V-domain linker. A molecular model showing the spatial orientation of the two epitopes is consistent with this observation. Linkers that incorporated helical domains (A[EAAAK](nA resulted in more effective DVD-Igs than those based solely on flexible domains ([GGGGS](n. In general, the DVD-Igs outperformed the less effective parental antibody and equaled the activity of the more effective. The ability of the DVD-Igs to deliver cytotoxic immunoconjugates in the absence of soluble CD4 was improved over that of either parent. CONCLUSIONS: DVD-Igs can be designed that bind to both gp120 and gp41 on the HIV envelope. DVD-Igs are effective in delivering cytotoxic immunoconjugates. The optimal design of these DVD-Igs, in which both domains are fully functional, has not yet been achieved.

  10. Association between immunoglobulin GM and KM genotypes and placental malaria in HIV-1 negative and positive women in western Kenya.

    Directory of Open Access Journals (Sweden)

    Nnaemeka C Iriemenam

    Full Text Available Immunoglobulin (Ig GM and KM allotypes, genetic markers of γ and κ chains, are associated with humoral immune responsiveness. Previous studies have shown the relationships between GM6-carrying haplotypes and susceptibility to malaria infection in children and adults; however, the role of the genetic markers in placental malaria (PM infection and PM with HIV co-infection during pregnancy has not been investigated. We examined the relationship between the gene polymorphisms of Ig GM6 and KM allotypes and the risk of PM infection in pregnant women with known HIV status. DNA samples from 728 pregnant women were genotyped for GM6 and KM alleles using polymerase chain reaction-restriction fragment length polymorphism method. Individual GM6 and KM genotypes and the combined GM6 and KM genotypes were assessed in relation to PM in HIV-1 negative and positive women, respectively. There was no significant effect of individual GM6 and KM genotypes on the risk of PM infection in HIV-1 negative and positive women. However, the combination of homozygosity for GM6(+ and KM3 was associated with decreased risk of PM (adjusted OR, 0.25; 95% CI, 0.08-0.8; P = 0.019 in HIV-1 negative women while in HIV-1 positive women the combination of GM6(+/- with either KM1-3 or KM1 was associated with increased risk of PM infection (adjusted OR, 2.10; 95% CI, 1.18-3.73; P = 0.011. Hardy-Weinberg Equilibrium (HWE tests further showed an overall significant positive F(is (indication of deficit in heterozygotes for GM6 while there was no deviation for KM genotype frequency from HWE in the same population. These findings suggest that the combination of homozygous GM6(+ and KM3 may protect against PM in HIV-1 negative women while the HIV-1 positive women with heterozygous GM6(+/- combined with KM1-3 or KM1 may be more susceptible to PM infection. The deficit in heterozygotes for GM6 further suggests that GM6 could be under selection likely by malaria infection.

  11. T-2 toxin impairment of enteric reovirus clearance in the mouse associated with suppressed immunoglobulin and IFN-γ responses

    International Nuclear Information System (INIS)

    Li Maoxiang; Cuff, Christopher F.; Pestka, James J.

    2006-01-01

    Trichothecenes are exquisitely toxic to the gastrointestinal (GI) tract and leukocytes and thus are likely to impair gut immunity. The purpose of this research was to test the hypothesis that the Type A trichothecene T-2 toxin interferes with the gut mucosal immune response to enteric reovirus infection. Mice were exposed i.p. first to 1.75 mg/kg bw T-2 and then 2 h later with 3 x 10 7 plaque-forming units of reovirus serotype 1, strain Lang (T1/L). As compared to vehicle-treated control, T-2-treated mice had dramatically elevated intestinal plaque-forming viral titers after 5 days and failed to completely clear the virus from intestine by 10 days. Levels of reovirus λ2 core spike (L2 gene) RNA in feces in T-2-treated mice were significantly higher at 1, 3, 5, and 7 days than controls. T-2 potentiated L2 mRNA expression in a dose-dependent manner with as little as 50 μg/kg of the toxin having a potentiative effect. T-2 exposure transiently suppressed induction of reovirus-specific IgA in feces (6 and 8 days) as well as specific IgA and IgG 2a in serum (5 days). This suppression corresponded to decreased secretion of reovirus-specific IgA and IgG 2a in Peyer's patch (PP) and lamina propria fragment cultures prepared 5 days after infection. T-2 suppressed IFN-γ responses in PP to reovirus at 3 and 7 days as compared to infected controls whereas IL-2 mRNA concentrations were unaffected. PP IL-6 mRNA levels were increased 2-fold 2 h after T-2 treatment, but no differences between infected T-2-exposed and infected vehicle-treated mice were detectable over the next 7 days. Overall, the results suggest that T-2 toxin increased both the extent of GI tract reovirus infection and fecal shedding which corresponded to both suppressed immunoglobulin and IFN-γ responses

  12. Trib1 Is Overexpressed in Systemic Lupus Erythematosus, While It Regulates Immunoglobulin Production in Murine B Cells

    Directory of Open Access Journals (Sweden)

    Léa Simoni

    2018-03-01

    Full Text Available Systemic lupus erythematosus (SLE is a severe and heterogeneous autoimmune disease with a complex genetic etiology, characterized by the production of various pathogenic autoantibodies, which participate in end-organ damages. The majority of human SLE occurs in adults as a polygenic disease, and clinical flares interspersed with silent phases of various lengths characterize the usual evolution of the disease in time. Trying to understand the mechanism of the different phenotypic traits of the disease, and considering the central role of B cells in SLE, we previously performed a detailed wide analysis of gene expression variation in B cells from quiescent SLE patients. This analysis pointed out an overexpression of TRIB1. TRIB1 is a pseudokinase that has been implicated in the development of leukemia and also metabolic disorders. It is hypothesized that Trib1 plays an adapter or scaffold function in signaling pathways, notably in MAPK pathways. Therefore, we planned to understand the functional significance of TRIB1 overexpression in B cells in SLE. We produced a new knock-in model with B-cell-specific overexpression of Trib1. We showed that overexpression of Trib1 specifically in B cells does not impact B cell development nor induce any development of SLE symptoms in the mice. By contrast, Trib1 has a negative regulatory function on the production of immunoglobulins, notably IgG1, but also on the production of autoantibodies in an induced model. We observed a decrease of Erk activation in BCR-stimulated Trib1 overexpressing B cells. Finally, we searched for Trib1 partners in B cells by proteomic analysis in order to explore the regulatory function of Trib1 in B cells. Interestingly, we find an interaction between Trib1 and CD72, a negative regulator of B cells whose deficiency in mice leads to the development of autoimmunity. In conclusion, the overexpression of Trib1 could be one of the molecular pathways implicated in the negative regulation

  13. Changes in spatiotemporal gait parameters following intravenous immunoglobulin treatment for chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Vo, Mary L; Chin, Russell L; Miranda, Caroline; Latov, Norman

    2017-10-01

    Gait impairment is a common presenting symptom in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). However, gait parameters have not previously been evaluated in detail as potential independent outcome measures. We prospectively measured changes in spatiotemporal gait parameters of 20 patients with CIDP at baseline and following treatment with intravenous immunoglobulin (IVIG), using GAITRite® a computerized walkway system with embedded sensors. Overall, study patients showed significant improvements in gait velocity, cadence, stride length, double support time, stance phase, and swing phase following IVIG treatment. Mean changes in velocity, stance phase, and swing phase, exhibited the greatest statistical significance among the subgroup that exhibited clinically meaningful improvement in Inflammatory Neuropathy Cause and Treatment disability score, Medical Research Council sum score, and grip strength. Assessment of gait parameters, in particular velocity, step phase and swing phase, is a potentially sensitive outcome measure for evaluating treatment response in CIDP. Muscle Nerve 56: 732-736, 2017. © 2017 Wiley Periodicals, Inc.

  14. Immunoglobulins acquire the ability to interact with DNA after chromatography on QAE-Sephadex

    International Nuclear Information System (INIS)

    Sulaeva, N.I.; Lekakh, I.V.; Poverennyi, A.M.

    1986-01-01

    It was established that IgG isolated from the sera of healthy humans contains a substantial number of antibodies that react with native DNA. Their ability to interact with DNA is manifested only after chromatography on an anion exchange resin, as a result of which IgG is divided into two portions - acid and basic immunoglobulins. The peculiarities of the interaction of both fractions with DNA and the specificity of this reaction were investigated. It was shown that the investigated IgG can react with native and denatured DNA, dextran sulfate, poly(G), and poly(I). The question of the possibility of the interaction of the antibodies studied with the charged structures of the cell and that of the role of these antibodies in the normal and pathological states are discussed

  15. Successful Immunoglobulin Treatment in Severe Cryptogenic Organizing Pneumonia Caused by Dermatomyositis

    Directory of Open Access Journals (Sweden)

    Dong Hoon Lee

    2015-08-01

    Full Text Available In connective tissue diseases, autoantibodies cause pulmonary interstitial inflammation and fibrosis, and patients require treatment with an immunosuppressive agent such as a steroid. Dermatomyositis is an incurable, uncommon form of connective tissue disease that occasionally causes diffuse pulmonary inflammation leading to acute severe respiratory failure. In such cases, the prognosis is very poor despite treatment with high-dose steroid. In the present case, a 46-year-old man was admitted to our hospital with dyspnea. He was diagnosed with dermatomyositis combined with cryptogenic organizing pneumonia (COP with respiratory failure and underwent treatment with steroid and an immunosuppressive agent, but the COP was not improved. However, the respiratory failure did improve after treatment with intravenous immunoglobulin, which therefore can be considered a treatment option in cases where steroids and immunosuppressive agents are ineffective.

  16. Unilateral Oral Mucous Membrane Pemphigoid: Refractory Atypical Presentation Successfully Treated with Intravenous Immunoglobulins

    Directory of Open Access Journals (Sweden)

    André Laureano

    2015-01-01

    Full Text Available A 57-year-old male presented with a 6-month history of blisters and painful erosions on the right buccal mucosa. No skin or other mucosal involvement was seen. The findings of histopathological and direct immunofluorescence examinations were sufficient for the diagnosis of oral mucous membrane pemphigoid in the context of adequate clinical correlation. No response was seen after topical therapies and oral corticosteroids or dapsone. Intravenous immunoglobulin was started and repeated every three weeks. Complete remission was achieved after three cycles and no recurrence was seen after two years of follow-up. The authors report a rare unilateral presentation of oral mucous membrane pemphigoid on the right buccal and hard palate mucosa, without additional involvement during a period of five years. Local trauma or autoimmune factors are possible etiologic factors for this rare disorder, here with unique presentation.

  17. Radiologic Findings of Immunoglobulin G4 Related Sclerosing Esophagitis: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Sun; Kim, Su Young; Lee, Byung Hoon; Hwang, Yoon Joon; Han, Yoon Hee [Dept. of Radiology, Ilsan Paik Hospital, Inje University College of Medicine, Koyang (Korea, Republic of)

    2012-02-15

    We describe a case of immunoglobulin G4 (IgG4)-related sclerosing esophagitis occurring in a 63-year-old man with progressive dysphagia and 10-kg weight loss over 9 months. An esophagoscopy revealed significant stricture with diffuse mucosal friability and ulceration at mid esophagus level. Barium esophagogram showed diffuse stenosis at the mid and lower esophagus levels with ulcerations and irregularity of the mucosa. Multidetector computed tomography revealed diffuse edematous and circumferential thickening of the submucosa and muscle layer of this esophageal segment. Fluorine 18 fluorodeoxyglucose positron emission tomography (FDG PET) revealed diffuse mild FDG uptake in mid to lower esophagus. Although benign inflammatory lesion was suspected based on the imaging findings, the patient underwent surgery for worsening esophageal stricture and the esophageal lesion was pathologically confirmed as IgG4-related sclerosing esophagitis. Radiologic benignancy and high clinical suspicion for IgG4-related sclerosing disease may help making a proper decision and avoiding unnecessary operation.

  18. Immunoglobulin E antibodies to pollens augmented in dogs by virus vaccines.

    Science.gov (United States)

    Frick, O L; Brooks, D L

    1983-03-01

    An inbred "atopic dog colony" was established to study the effect of viruses on immunoregulation of immunoglobulin (Ig) E antibodies. Dogs were selected for high skin reactivity to grass and weed pollens. Their offspring were inoculated with pollen extracts in alum immediately after routine vaccinations (attenuated live-virus vaccines for canine distemper and infectious canine hepatitis, and a killed bacterin for Leptospira). Heat labile antipollen IgE antibodies were measured by passive cutaneous anaphylaxis. Pups vaccinated for canine distemper before being given pollen extracts had many more IgE antibodies than did their control littermates who were not vaccinated until after the last pollen extract injection. This may be a natural example of the "allergic break-through phenomenon."

  19. Measles Virus Neutralizing Antibodies in Intravenous Immunoglobulins: Is an Increase by Revaccination of Plasma Donors Possible?

    Science.gov (United States)

    Modrof, Jens; Tille, Björn; Farcet, Maria R; McVey, John; Schreiner, Jessica A; Borders, Charles M; Gudino, Maria; Fitzgerald, Peter; Simon, Toby L; Kreil, Thomas R

    2017-11-15

    We report a screen of plasma donors confirming that widespread use of childhood measles vaccination since 1963 resulted in a decrease in average measles virus antibody titers among plasma donors, which is reflected in intravenous immunoglobulins (IVIGs). The measles virus antibody titer, however, is a potency requirement for IVIGs, as defined in a Food and Drug Administration regulation. To mitigate the decline in measles virus antibody titers in IVIGs and to ensure consistent product release, revaccination of plasma donors was investigated as a means to boost titers. However, revaccination-induced titer increases were only about 2-fold and short-lived. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  20. Application of enhanced electronegative multimodal chromatography as the primary capture step for immunoglobulin G purification.

    Science.gov (United States)

    Wang, Yanli; Chen, Quan; Xian, Mo; Nian, Rui; Xu, Fei

    2018-06-01

    In recent studies, electronegative multimodal chromatography with Eshmuno HCX was demonstrated to be a highly promising recovery step for direct immunoglobulin G (IgG) capture from undiluted cell culture fluid. In this study, the binding properties of HCX to IgG at different pH/salt combinations were systematically studied, and its purification performance was significantly enhanced by lowering the washing pH and conductivity after high capacity binding of IgG under its optimal conditions. A single polishing step gave an end-product with non-histone host cell protein (nh-HCP) below 1 ppm, DNA less than 1 ppb, which aggregates less than 0.5% and an overall IgG recovery of 86.2%. The whole non-affinity chromatography based two-column-step process supports direct feed loading without buffer adjustment, thus extraordinarily boosting the overall productivity and cost-savings.

  1. Intravenous Immunoglobulins: Mode of Action and Indications in Autoimmune and Inflammatory Dermatoses

    Directory of Open Access Journals (Sweden)

    Lyubomir A. Dourmishev

    2016-01-01

    Full Text Available Intravenous immunoglobulins (IVIGs, a mixture of variable amounts of proteins (albumin, IgG, IgM, IgA, and IgE antibodies, as well as salt, sugar, solvents, and detergents, are successfully used to treat a variety of dermatological disorders. For decades, IVIGs have been administered for treatment of infectious diseases and immune deficiencies, since they contain natural antibodies that represent a first-line defense against pathogens. Today their indication has expanded, including the off-label therapy for a variety of autoimmune and inflammatory diseases. In dermatology, IVIGs are administered for treatment of different disorders at different therapeutic regimens, mostly with higher doses then those administered for treatment of infectious diseases. The aim of this prospective review is to highlight the indications, effectiveness, side effects, and perspectives of the systemic treatment with IVIGs for patients with severe, life-threatening, and resistant to conventional therapies autoimmune or inflammatory dermatoses.

  2. Scleromyxedema with Subcutaneous Nodules: Successful Treatment with Thalidomide and Intravenous Immunoglobulin

    Directory of Open Access Journals (Sweden)

    M. Dolenc-Voljč

    2013-11-01

    Full Text Available Scleromyxedema is a rare cutaneous mucinosis, usually presenting with generalized papular eruption and sclerodermoid induration, monoclonal gammopathy and systemic manifestations. An atypical clinical presentation with cutaneous and subcutaneous nodules has been reported rarely. In recent years, intravenous immunoglobulin (IVIg appears to be the therapy of choice for scleromyxedema. Treatment experiences in atypical manifestations with mucinous nodules are limited to sporadic reports. We report the case of male patient with atypical scleromyxedema without underlying paraproteinemia, presenting with generalized papular and sclerodermoid skin eruption and multiple nodular mucinous lesions on the fingers and face as well as on the eyelids, and associated systemic symptoms. Complete regression of all cutaneous lesions and extracutaneous symptoms with sustained remission was achieved by combined treatment with thalidomide and IVIg.

  3. Scleromyxedema with Subcutaneous Nodules: Successful Treatment with Thalidomide and Intravenous Immunoglobulin

    Science.gov (United States)

    Dolenc-Voljč, M.; Jurčić, V.; Hočevar, A.; Tomšič, M.

    2013-01-01

    Scleromyxedema is a rare cutaneous mucinosis, usually presenting with generalized papular eruption and sclerodermoid induration, monoclonal gammopathy and systemic manifestations. An atypical clinical presentation with cutaneous and subcutaneous nodules has been reported rarely. In recent years, intravenous immunoglobulin (IVIg) appears to be the therapy of choice for scleromyxedema. Treatment experiences in atypical manifestations with mucinous nodules are limited to sporadic reports. We report the case of male patient with atypical scleromyxedema without underlying paraproteinemia, presenting with generalized papular and sclerodermoid skin eruption and multiple nodular mucinous lesions on the fingers and face as well as on the eyelids, and associated systemic symptoms. Complete regression of all cutaneous lesions and extracutaneous symptoms with sustained remission was achieved by combined treatment with thalidomide and IVIg. PMID:24348379

  4. Antibody modeling using the prediction of immunoglobulin structure (PIGS) web server [corrected].

    Science.gov (United States)

    Marcatili, Paolo; Olimpieri, Pier Paolo; Chailyan, Anna; Tramontano, Anna

    2014-12-01

    Antibodies (or immunoglobulins) are crucial for defending organisms from pathogens, but they are also key players in many medical, diagnostic and biotechnological applications. The ability to predict their structure and the specific residues involved in antigen recognition has several useful applications in all of these areas. Over the years, we have developed or collaborated in developing a strategy that enables researchers to predict the 3D structure of antibodies with a very satisfactory accuracy. The strategy is completely automated and extremely fast, requiring only a few minutes (∼10 min on average) to build a structural model of an antibody. It is based on the concept of canonical structures of antibody loops and on our understanding of the way light and heavy chains pack together.

  5. Cell Adhesion Molecules of the Immunoglobulin Superfamily in the Nervous System

    DEFF Research Database (Denmark)

    Walmod, Peter Schledermann; Pedersen, Martin Volmer; Berezin, Vladimir

    2007-01-01

    Cell adhesion molecules (CAMs) are proteins mediating cell-cell or cell-extracellular matrix (ECM) interactions. CAMs are traditionally divided into four groups, the cadherins, the selectins, the integrins and CAMs belonging to the immunoglobulin superfamily (IgSF). The present chapter describes...... CAMs belonging to IgSF, that exclusively or in part, are expressed in the nervous system. The chapter includes descriptions of myelin protein zero (P0), integrin-associated protein (CD47), neuroplastin, activated leukocyte-cell adhesion molecule (ALCAM), melanoma cell adhesion molecule (MCAM......), myelinassociated glycoprotein (MAG), the neural cell adhesion molecules 1 and 2 (NCAM, NCAM2), Down Syndrome cell adhesion molecule (DSCAM) and Down Syndrome cell adhesion molecule-like-1 (DSCAML1), sidekick 1 and 2 (SDK1, SDK2), signal-regulatory proteins (SIRPs), nectins, nectin-like proteins (necls...

  6. Phosphine reduced IgG. A new method for 99mTc labeling immunoglobulins

    International Nuclear Information System (INIS)

    Arteaga de Murphy, C.; Melendez-Alafort, L.; Martinez-Rivero, O.; Gomez, E.; Ferro-Flores, G.

    1997-01-01

    A new technetium labeling method for immunoglobulins reduced with tris(2-carboxy-ethyl)phosphine hydrochloride is presented. The Sandoglobulina IgG source was assayed for purity and optimum reagent's concentration and incubation times were determined. It was purified by column chromatography and labelled with Sn 2+ reduced technetium in the presence of MDP. The kit is easy to prepare, labeling efficiency is >(97±1.9)% and stable for 6 hours.The immunoreactivity of the 99 Tc-IgG was verified by electrophoresis and Western blot tests. The IgG retained its structure after both the reducing and labeling processes and it was the only labeled species. (author)

  7. Immunoglobulin G4-related tubulointerstitial nephritis: A not to be missed diagnosis

    Directory of Open Access Journals (Sweden)

    Smita Mary Matthai

    2017-01-01

    Full Text Available Immunoglobulin G4-related tubulointerstitial nephritis (IgG4-TIN is a newly recognized clinicopathological entity characterized by a dense interstitial infiltrate of IgG4-positive plasma cells accompanied by fibrosis and obliterative phlebitis causing acute or chronic renal dysfunction amenable to corticosteroid therapy. IgG4-TIN is the dominant manifestation of renal involvement in IgG4-related disease (IgG4-RD which is a novel, immune-mediated, fibroinflammatory and multiorgan disorder. We describe a case of IgG4-TIN with isolated renal involvement in an elderly male patient with poor response to corticosteroid therapy. The distinctive serological, histopathological, and ultrastructural features of this condition which can facilitate differential diagnosis of TIN are highlighted to emphasize the need for early diagnosis and preservation of kidney function.

  8. Non-ST Elevation Myocardial Infraction after High Dose Intravenous Immunoglobulin Infusion

    Directory of Open Access Journals (Sweden)

    Meir Mizrahi

    2009-01-01

    Full Text Available Intravenous immunoglobulins (IVIgs are used for several indications, including autoimmune conditions. IVIg treatment is associated with several possible adverse reactions including induction of a hypercoagulable state. We report a 76-year-old woman treated with IVIg for myasthenia gravis, which developed chest pain and weakness following IVIg infusion. The symptoms were associated with ST segment depression in V4–6 and elevated troponin levels. The patient was diagnosed with non-ST elevation myocardial infarction (NSTEMI. The patient had no significant risk factor besides age and a cardiac perfusion scan was interpreted as normal (the patient refused to undergo cardiac catheterization. This case is compatible with IVIg-induced hypercoagulability resulting in NSTEMI. Cardiac evaluation should therefore be considered prior to initiation of IVIg treatment especially in patients with multiple cardiovascular risks.

  9. Characteristics and Long-Term Outcome of Patients with Systemic Immunoglobulin Light-Chain Amyloidosis

    DEFF Research Database (Denmark)

    Nelson, Lærke Marie; Gustafsson, Finn; Gimsing, Peter

    2015-01-01

    Background/Aims: Immunoglobulin light-chain (AL) amyloidosis is a systemic disorder that causes progressive organ dysfunction. The optimal treatment strategy requires accurate patient stratification with an emphasis on the extent of cardiac involvement. Reports on its prognosis are sparse...... and predominantly originate from highly selected centers. We aimed to evaluate patient characteristics and outcomes in a cohort treated at a single center. Methods: This is a single-center retrospective study of 63 consecutive patients diagnosed with AL amyloidosis between January 2000 and December 2012. Patients...... were evaluated by treatment strategy and cardiac involvement. Results: The mean age at diagnosis was 61.4 years (±8.9), and 39 patients (62%) were male. Thirty-two (51%) patients presented with cardiac amyloid involvement (CA) and the remaining 31 (49%) had noncardiac amyloidosis (NCA). The median...

  10. Thyroid Stimulating Immunoglobulin Bioassay Using Cultured Human Thyroid Cells; A Simplified Micromethod

    International Nuclear Information System (INIS)

    Lee, Myung Chul; Chung, June Key; Cho, Bo Youn; Koh, Chang Soon; Lee, Moon Ho; Ahn, Il Min; Ahn, Hee Kwon

    1985-01-01

    The activation of adenylate cyclase of human thymocytes in primary cell culture and the release of c-AMP into the medium are used to detect b-TSH and TSAb in sera of patients with autoimmune thyroid disease. Sera of patients are used directly as a part of cell culture without immunoglobulin precipitation. In the above TSI bioassay, TSAb pooled serum show c-AMP concentration between that of 1 mU/ml and 10 mU/ml b-TSH but normal control pooled serum doesn't show any detectable c-AMP response. Ninety five percent of untreated Graves' patients shows TSAb activity above normal range, 20% of Hashimoto's and 363/0 of euthyroid Graves' patients show detectable TSAb activity.

  11. Effects of radioiodine on thyrotrophin binding inhibiting immunoglobulins in Graves' disease

    International Nuclear Information System (INIS)

    McGregor, A.M.; Petersen, M.M.; Capiferri, R.; Evered, D.C.; Rees Smith, B.; Hall, R.

    1979-01-01

    The effects of 131 I therapy on thyrotrophin binding inhibiting immunoglobulins (TBII) were studied in fifty-five patients with Graves' disease and five patients with toxic multinodular goitre (MNG). A group of forty patients with Graves' disease and four patients with toxic MNG were treated with drugs and acted as controls. In 78% of patients treated with 131 I there was a dramatic increase in serum TBII activity during the 3 months following therapy, whereas drug-treated patients showed a decrease (77%) or no change in TBII activity over the same period. TBII activity was not detectable in patients with toxic MNG before or after drug or 131 I therapy. Consideration of the mechanisms involved in the changes in serum TBII activity after 131 I treatment or during drug treatment provide insight into the basic defects responsible for the development of Graves' disease and suggest that both the thyroid and immune system are involved. (author)

  12. Immunoglobulin G antibodies against Porphyromonas gingivalis or Aggregatibacter actinomycetemcomitans in cardiovascular disease and periodontitis

    DEFF Research Database (Denmark)

    Damgaard, Christian; Reinholdt, Jesper; Enevold, Christian

    2017-01-01

    Objectives: The aim was to elucidate whether levels of circulating antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis correlate to loss of attachment, as a marker for periodontitis and cardiovascular disease (CVD). Design: Sera were collected from 576 participants...... of the Danish Health Examination Survey (DANHES). Immunoglobulin G antibodies against lipopolysaccharide (LPS) and protein antigens from the a, b and c serotypes of A. actinomycetemcomitans and P. gingivalis were quantified by titration in ELISA plates coated with a mixture of antigens prepared...... by disintegration of bacteria. Results: Levels of antibodies against P. gingivalis (OR = 1.48) and A. actinomycetemcomitans (1.31) associated with periodontitis, as determined by univariable logistic regression analysis. These antibody levels also associated with CVD (1.17 and 1.37), respectively, However, after...

  13. Method for the isolation of biologically active monomeric immunoglobulin A from a plasma fraction.

    Science.gov (United States)

    Leibl, H; Tomasits, R; Wolf, H M; Eibl, M M; Mannhalter, J W

    1996-04-12

    A purification method for immunoglobulin A (IgA) yielding monomeric IgA with a purity of over 97% has been developed. This procedure uses ethanol-precipitated plasma (Cohn fraction III precipitate) as the starting material and includes heparin-Sepharose adsorption, dextran sulfate and ammonium sulfate precipitation, hydroxyapatite chromatography, batch adsorption by an anion-exchange matrix and gel permeation. Additional protein G Sepharose treatment leads to an IgA preparation of greater than 99% purity. The isolated IgA presented with an IgA subclass distribution, equivalent to IgA in unfractionated plasma, and was biologically active, as was shown by its ability to down-modulate Haemophilus influenzae-b-induced IL-6 secretion of human monocytes.

  14. ε-Polylysine-based thermo-responsive adsorbents for immunoglobulin adsorption-desorption under mild conditions.

    Science.gov (United States)

    Maruyama, Masashi; Shibuya, Keisuke

    2017-08-22

    Thermo-responsive adsorbents for immunoglobulin G (IgG) employing ε-polylysine (EPL) as a polymer backbone were developed. The introduction of mercaptoethylpyridine (MEP) as an IgG-binding ligand and hydrophobization of side chains afforded thermo-responsive IgG adsorbents, whose thermo-responsive IgG desorption ratio was up to 88% (EPL/MEP derivative 3m). The changes in surface densities of active MEP groups, which are caused by thermal conformational changes of the adsorbents, play key roles for IgG desorption. Although a trade-off of IgG adsorption capacity and IgG desorption ratio was observed, the present study offers a novel molecular design for thermo-responsive adsorbents with high synthetic accessibility and potentially low toxicity.

  15. INTRAVENOUS IMMUNOGLOBULIN ADMINISTRATION FOR DESENSITIZATION BEFORE RENAL TRANSPLANTATION AND MANAGING ANTIBODY-MEDIATED REJECTION

    Directory of Open Access Journals (Sweden)

    A. I. Sushkov

    2011-01-01

    Full Text Available Much attention has been placed recently in transplantation in highly HLA-sensitized patients. In attempts to remove these antibodies and enable successful renal transplantation, several approaches have been developed. Intravenous immunoglobulin (IVIG was found to be effective in the treatment of autoimmune and inflammatory disorders (e. g. Kawasaki disease, Guillain-Barre syndrome. Recently, a beneficial effect of IVIG on the reduc- tion of anti-HLA antibodies was described. The anti-inflammatory effect of IVIG provides hopeful opportunities in antibody-mediated rejection (AMR management. There are several protocols of IVIG administration for pre-transplant desensitization and AMR treatment: high-dose IVIG, low-dose IVIG + plasmapheresis, IVIG + plasmapheresis + rituximab. These advancements have enabled transplantation in patients previously considered untransplantable and in concert with new diagnostic techniques has resulted in new approaches to management of AMR. 

  16. Anti-ghrelin immunoglobulins modulate ghrelin stability and its orexigenic effect in obese mice and humans

    Science.gov (United States)

    Takagi, Kuniko; Legrand, Romain; Asakawa, Akihiro; Amitani, Haruka; François, Marie; Tennoune, Naouel; Coëffier, Moïse; Claeyssens, Sophie; do Rego, Jean-Claude; Déchelotte, Pierre; Inui, Akio; Fetissov, Sergueï O.

    2013-01-01

    Obese individuals often have increased appetite despite normal plasma levels of the main orexigenic hormone ghrelin. Here we show that ghrelin degradation in the plasma is inhibited by ghrelin-reactive IgG immunoglobulins, which display increased binding affinity to ghrelin in obese patients and mice. Co-administration of ghrelin together with IgG from obese individuals, but not with IgG from anorectic or control patients, increases food intake in rats. Similarly, chronic injections of ghrelin together with IgG from ob/ob mice increase food intake, meal frequency and total lean body mass of mice. These data reveal that in both obese humans and mice, IgG with increased affinity for ghrelin enhances ghrelin’s orexigenic effect, which may contribute to increased appetite and overeating. PMID:24158035

  17. Equine Immunoglobulin and Equine Neutralizing F(ab')₂ Protect Mice from West Nile Virus Infection.

    Science.gov (United States)

    Cui, Jiannan; Zhao, Yongkun; Wang, Hualei; Qiu, Boning; Cao, Zengguo; Li, Qian; Zhang, Yanbo; Yan, Feihu; Jin, Hongli; Wang, Tiecheng; Sun, Weiyang; Feng, Na; Gao, Yuwei; Sun, Jing; Wang, Yanqun; Perlman, Stanley; Zhao, Jincun; Yang, Songtao; Xia, Xianzhu

    2016-12-18

    West Nile virus (WNV) is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to prevent WNV disease. In this study, we prepared and evaluated the protective efficacy of immune serum IgG and pepsin-digested F(ab')₂ fragments from horses immunized with the WNV virus-like particles (VLP) expressing the WNV M and E proteins. Immune equine F(ab')₂ fragments and immune horse sera efficiently neutralized WNV infection in tissue culture. The passive transfer of equine immune antibodies significantly accelerated the virus clearance in the spleens and brains of WNV infected mice, and reduced mortality. Thus, equine immunoglobulin or equine neutralizing F(ab')₂ passive immunotherapy is a potential strategy for the prophylactic or therapeutic treatment of patients infected with WNV.

  18. Equine Immunoglobulin and Equine Neutralizing F(ab′2 Protect Mice from West Nile Virus Infection

    Directory of Open Access Journals (Sweden)

    Jiannan Cui

    2016-12-01

    Full Text Available West Nile virus (WNV is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to prevent WNV disease. In this study, we prepared and evaluated the protective efficacy of immune serum IgG and pepsin-digested F(ab′2 fragments from horses immunized with the WNV virus-like particles (VLP expressing the WNV M and E proteins. Immune equine F(ab′2 fragments and immune horse sera efficiently neutralized WNV infection in tissue culture. The passive transfer of equine immune antibodies significantly accelerated the virus clearance in the spleens and brains of WNV infected mice, and reduced mortality. Thus, equine immunoglobulin or equine neutralizing F(ab′2 passive immunotherapy is a potential strategy for the prophylactic or therapeutic treatment of patients infected with WNV.

  19. An aortoduodenal fistula as a complication of immunoglobulin G4-related disease

    Science.gov (United States)

    Sarac, Momir; Marjanovic, Ivan; Bezmarevic, Mihailo; Zoranovic, Uros; Petrovic, Stanko; Mihajlovic, Miodrag

    2012-01-01

    Most primary aortoduodenal fistulas occur in the presence of an aortic aneurysm, which can be part of immunoglobulin G4 (IgG4)-related sclerosing disease. We present a case who underwent endovascular grafting of an aortoduodenal fistula associated with a high serum IgG4 level. A 56-year-old male underwent urgent endovascular reconstruction of an aortoduodenal fistula. The patient received antibiotics and other supportive therapy, and the postoperative course was uneventful, however, elevated levels of serum IgG, IgG4 and C-reactive protein were noted, which normalized after the introduction of steroid therapy. Control computed tomography angiography showed no endoleaks. The primary aortoduodenal fistula may have been associated with IgG4-related sclerosing disease as a possible complication of IgG4-related inflammatory aortic aneurysm. Endovascular grafting of a primary aortoduodenal fistula is an effective and minimally invasive alternative to standard surgical repair. PMID:23155348

  20. Membranous glomerulopathy and massive cervical lymphadenopathy due to immunoglobulin G4-disease

    Directory of Open Access Journals (Sweden)

    Kamel El-Reshaid

    2017-01-01

    Full Text Available A 32-year-old male presented with acute and severe nephrotic syndrome as well as massive right cervical lymphadenopathy for <2 years. Computed tomography scan of the chest, abdomen, and pelvis did not reveal any lymphadenopathy. Histopathology and immunohistochemical testing of his lymph node biopsy showed infiltrate enriched with immunoglobulin G4 (IgG4-positive plasma cells. His kidney biopsy showed granular membranous deposits of IgG4 in the basement membrane without interstitial infiltrate. Antiphospholipid 2 receptor antibodies were absent excluding its "idiopathic" nature. Since he was allergic to rituximab, he was treated with corticosteroids for two months and a combination of tacrolimus and mycophenolate. His lymphadenopathy disappeared, and his proteinuria abated. The dose of the latter two medications was reduced to half after four months and will be maintained for a minimum of two years to prevent relapse of his disease.